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  • Jozef Rovenský
  • Juraj Payer
  • Manfred Herold
Chapter
  • 629 Downloads

Abstract

Ibandronate A bisphosphonate licensed for the treatment of postmenopausal osteoporosis. The drug can be administered orally or by slow intravenous injection. Orally, it is given before meals and washed down with a cup of water; afterwards, the patient must sit and not lie down for 30 min. The oral dose of 150 mg is given once a month, a regimen thought to improve compliance. It can also be administered by slow intravenous injection at a dose of 3 mg in 3ml every 3 months. This is particularly useful in patients with gastrointestinal intolerance of bisphosphonates.

Keywords

Systemic Lupus Erythematosus Idiopathic Pulmonary Fibrosis Williams Syndrome Inclusion Body Myositis Idiopathic Inflammatory Myopathy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Ibandronate A bisphosphonate licensed for the treatment of postmenopausal osteoporosis. The drug can be administered orally or by slow intravenous injection. Orally, it is given before meals and washed down with a cup of water; afterwards, the patient must sit and not lie down for 30 min. The oral dose of 150 mg is given once a month, a regimen thought to improve compliance. It can also be administered by slow intravenous injection at a dose of 3 mg in 3ml every 3 months. This is particularly useful in patients with gastrointestinal intolerance of bisphosphonates.

ICAM – see Intercellular adhesion molecule (ICAM).

ICF – see International classification of functioning (ICF).

Idiopathic infantile hypercalcaemia Patients resemble children with Williams syndrome; some of them can have heart disease, facial dysmorphism, hypertension and radioulnar synostosis. Further, there can be strabismus (squint), inguinal hernia and hyperacusis, which are persistent. Polyuria and polydipsia are frequent. In some patients, an elevated PTHrP (parathyroid hormone-related protein) level can be detected. The hypercalcaemia persists much longer than in Williams syndrome and sometimes requires limitation of the calcium intake, exclusion of vitamin D and administration of glucocorticoids.

Idiopathic inflammatory myopathies (IIM) Acquired inflammatory disorders of the striated muscles of unknown aetiology. They can be subdivided into primary idiopathic polymyositis (PM), primary idiopathic dermatomyositis (DM), PM–DM in childhood, myositis associated with malignancy and myositis combined with other systemic rheumatic disorders (such as scleroderma, systemic lupus erythematosus, Sjögren’s syndrome or rheumatoid arthritis). Certain other disorders are included such as inclusion body myositis (IBM), granulomatous myositis and eosinophilic myositis or focal and nodular myositis.
  • ► Clinical symptoms and signs

    Idiopathic inflammatory myopathies are characterised by the presence of symmetrical, predominantly proximal muscle weakness, biopsy evidence of muscle fibre impairment, elevated serum levels of muscle enzymes or myoglobin and the presence of multifocal myopathic signs on electromyography. In DM characteristic changes of the skin appear. Impairment of other systems such as the joints, lungs, heart and gastrointestinal tract occur with variable frequency. There may be an association with malignancy, especially in the older population.

Criteria of classification: Minimally modified criteria of Bohan and Peter are used and include the following manifestations:
  • Predominant or strictly proximal, usually symmetrical muscle weakness, progressive over weeks or months, with or without myalgias

  • Biopsy evidence of muscle fibre necrosis and regeneration with a mononuclear inflammatory infiltrate (perivascular or intravascular) with or without perifascicular atrophy

  • Elevated serum creatine kinase (MM-isoenzyme), aldolase and myoglobin levels

  • Multifocal myopathic changes on electromyography (small, short and polyphasic potentials) with increased insertion activity, with or without spontaneous potentials

  • A rash typical for DM, especially heliotropic exanthema and Gottron’s signs

A diagnosis of IIM is definite when 4 or more criteria are present; it is probable when three criteria are present.

A diagnosis of DM is definite in the presence of a rash and three other criteria; it is probable in the presence of a rash and two other criteria.
  • ► Laboratory tests

    Serum levels of creatine kinase (CK), lactate dehydrogenase, serum glutamic oxaloacetic (SGOT) or aspartate transaminase (AST), aldolase and myoglobin are raised. The rise occurs in the course of active disease and often normalises during remission. The level of MM-CK isoenzyme is especially elevated but also the MB-CK fraction which comes from a repeatedly damaged regenerating muscle. Occasionally the level of CK is normal due to the presence of inhibitors or in association with malignancy. Autoantibodies are present in the serum of 70–80 % of patients. The erythrocyte sedimentation rate (ESR) and acute phase proteins are often normal. Mild anaemia can be present. The autoantibodies probably play a role in the pathogenic process and often associate with other clinical signs (Table 1 ).
    Table 1

    Associations for myositis-specific autoantibodies

    Myositis-specific autoantibody

    Clinical picture

    Onset of myositis

    Response to treatment

    Prognosis

    HLA association*

    Frequency of incidence in myositis

    Rate

    Severity

    Season

    Antisynthetases (anti-Jo-1)

    Arthritis, interstitial pulmonary fibrosis, fever, ‘hand mechanics’, Raynaud’s phenomenon

    Acute

    Severe

    Spring

    Moderate, outbreak at dose decrement

    Poor, 5-year survival in 70 % of cases

    DR3

    DRw52

    DQA1*0501

    20–40 %

    Anti-SRP

    Cardiac involvement, myalgia

    Very acute

    Very severe

    Autumn

    Poor, aggressive chemotherapy needed

    Very poor, 5-year survival in 25 % of cases

    DR5

    DRw52

    DQA1*0301

    5 %

    Anti-Mi-2

    DM classification with a distribution of rash in the V- and shawl-shaped type

    Acute

    Mild

    Anytime

    Good, but the rash persists long

    Good, 5-year survival in almost 100 % of cases

    DR7

    DRw53

    DQA1*0201

    15–20 %

    Modified according to: Miller, JAMA, 270, (1993)

    DM dermatomyositis, SRP signal recognition particle

Idiotope An idiotope is a unique set of antigen determinants found in variable domains of immunoglobulin polypeptide chains.

Idiotype It is a shared characteristic between a group of immunoglobulin or T cell receptor (TCR) molecules based upon the antigen-binding specificity and therefore structure of their variable region. Also it is a set of idiotopes at the binding site for a certain antibody. Anti-idiotypic antibodies that are one’s own anti-antibodies can develop against the idiotypes. Their binding site is complementary to the binding site of the first antibodies and so it has a spatial structure identical to the antigen determinant that is specific for this first antibody. These anti-idiotypic antibodies are therefore referred to as the inner antigen picture of homoantibodies. It is assumed that the idiotypes and anti-idiotypes form a regulatory network in the body.

IgA A class of immunoglobulins whose molecules can exist in two forms, either serum IgA (a monomer) or secretory IgA (a dimer whose molecule also contains a J-chain and a secretory component SC). Secretory IgA (S-IgA) can be found in mucosal secretions where it participates in local immune reactions. Penetration of epithelial cells onto the surface of the mucous membrane is facilitated by the secretory component. There are two known isotypes of heavy chains α – α1 and α2 – which produce antibodies of IgA1 and IgA2 subclasses.

IgD Immunoglobulins with a less well-understood biological function. IgD molecules are, together with IgM monomers, most frequently incorporated in the cytoplasmic membrane of B lymphocytes, having a discriminative function of the antigen receptor component.

IgE In physiological circumstances, their serum concentration is the lowest of all immunoglobulins. These antibodies participate in the protection of the body against parasitic infections and, just like reagins, are responsible for early hypersensitive reactions (allergies, anaphylaxis). Serum IgE levels are raised in parasitic infections and are especially high in allergic reactions.

IGF – see Insulin-like growth factor (IGF).

IgG This class of immunoglobulins is the most widespread in extracellular fluids. Their molecules consist of two identical light and two identical heavy chains that are spatially organised into domains. There are four known heavy chains γ distinct in antigens, which form the four subclasses IgG1, IgG2, IgG3 and IgG4. The antibodies of IgG class are formed mainly during the response to the repeated administration of soluble antigens. They are the only antibodies to cross the human foetal–maternal barrier in the placenta. They activate complement after binding with the antigen (immune complexes) or in the form of self-aggregates (clusters of one’s own molecules).

IgM They have the biggest relative molecular weight (900,000 kDa) and sedimentation coefficient (19S). Their molecule consists of five identical subunits (each with 180 kDa and 8S), thus forming a pentamere that aside from 10 light chains and 10 heavy chains contains also one J-chain. A small amount of circulating IgM (up to 5 %) forms a hexamere. The basic subunit 8S of IgM is not circulating but remains in membrane form as a component of the antigen receptor on the surface of B lymphocytes. Antibodies belonging to the IgM class are produced mainly upon first contact of the organism with a corpuscular antigen. They have the greatest additive effect of multivalency, which makes them particularly effective in the agglutination of bacteria and in activating complement via the classical pathway (after formation of immune complexes or aggregates).

IIF (indirect immunofluorescence) A laboratory test used to detect antibodies in serum or other body fluids. IIF uses two antibodies. The primary antibody is unconjugated, and a fluorophore-conjugated secondary antibody directed against the primary antibody is used for detection. The IIF Test on Hep-2 cells is the recommended gold standard to detect antinuclear antibodies (ANAs).

IL 1–18 – see Interleukin 1–18.

IL-1R The IL-1 receptor occurs in two isotypes: I and II. Type II has a shorter cytoplasmic part compared to type I which consequently causes insufficient intracellular transmission of the signal after binding IL-1.

IL-1RA An antagonist of the IL-1 receptor. IL-1 is a cytokine participating in normal physiological processes as well as regulation of the inflammatory responses. IL-1RA occurs in three isoforms: one secretory (sIL-1RA) and two intracellular (icIL-1RAI and icIL-1RAII). The function of secretory IL1RA consists in local inhibition of IL-1 and blockade of acute phase proteins, whilst the function of the intracellular IL-1RA is unknown.

Immune complexes Complexes arising from the reaction between an antigen and an antibody. They can occur either in vitro (where they are the essence of immunochemical assays and diagnostic methods) or in vivo (in which case they facilitate phagocytosis of bacteria or other particles opsonised by the antibodies or can induce immune complex disorders if the immune complexes are soluble or autoimmune disorders when the reaction between an autoantibody and autoantigen occurs in an organ). With in vivo conditions or in the presence of blood serum, the immune complexes can also bind to certain components of complement.

Immune-mediated necrotising myopathy A subtype of a statin-induced myopathy, characterised by muscle fibre necrosis without presence of a significant lymphocytic inflammatory infiltrate. Pathogenesis is autoimmune. Antibodies against HMG CoAR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) are detected in patient serum. Discontinuation of a statin is not a sufficient therapy. Treatment consists of immunosuppression.

Immune system (IS) This is a diffuse (not strictly delineated) organ that weighs around 1000 g in an adult and consists of multiple tissues, cells and molecules. It is a component of the neuro–endocrine–immune supersystem, ensuring the input and processing of all information necessary for the survival of humans and other superior organisms. The fundament component of the IS is lymphatic tissue either condensed in lymphoid organs or existing in the form of free cells (lymphocytes, leukocytes). The lymphoid organs are divided into central (primary) or peripheral (secondary). As well as lymphocytes, the other important cells include antigen-presenting cells and phagocytes (especially macrophages and neutrophils). Essential molecules involved in the reactions of the IS include antibodies (immunoglobulins), components and factors of the complement system (complement), various immunohormones, cytokines and other immunoregulatory substances, and numerous receptors on the surface of immunologically active cells, such as antigen and immunoadherence receptors, Fc receptors etc. The basic function of the IS is to obtain information from the internal and external environment, their logical processing and response (immune response), the result of which is usually a defence-adaptation reaction (induction of immunity) but can also sometimes cause damage to one’s own tissues, cells and their structure in the autoimmune or other immunopathological responses (immunopathology). In this respect, the immune system is similar to the neuroendocrine system, with which it is closely linked, thus forming a single superinformation system that is a prerequisite for the existence of all superior animals. The most important property of the IS is its ability to differentiate its own molecular structures from foreign ones (antigen). Proper and fully functioning antigens are normally tolerated; heterogeneous (on the surface of microorganisms or transplanted cells) or proper but functionally altered (estranged as, e.g. on tumour-transformed or virus-infected cells) are inactivated and destroyed in the course of an immune response.

Immunity The capability of an organism to withstand infectious germs (viruses, bacteria, fungi, cytozoon), foreign and estranged cells (cells transplanted from a genetically different individual and one’s own altered cells (cancerous) or cells invaded by viruses) and their products, producing the ability to react against the antigen by the immune response to the benefit of the body. This immunity can be either non-specific (natural, innate) or specific (acquired, adaptive). Both are determined by an individual’s genetic makeup (genome).

Numerous anatomical structures (e.g. the skin and mucous membranes) and physiological systems (e.g. haemocoagulation) that are not directly part of the immune system (they represent a natural resistance), as well as specialised molecules (the complement system, many cytokines) and cellular mechanisms (phagocytosis) participate in non-specific immunity. The activity of innate immune mechanisms is not conditioned to prior sensitisation with a certain antigen, and so they are effective against various antigens and do not possess an immunological memory.

Contrary to these, the mechanisms of specific immunity are activated only after contact with a certain antigen and referred to as acquired or adaptive immunity. They are specific in acting only against the antigen that has activated it, possess immunological memory and are evolutionary younger than components of the natural immunity. Cells and molecules can participate in both non-specific and specific immunity. Phagocytosis and NK cells are basic mechanisms of non-specific cellular immunity, whilst the executive (cytotoxic) and regulatory (helper and suppressive) T lymphocytes are responsible for specific cellular immunity. The complement system (complement) is the most important component of non-specific humoural (molecular) immunity, whilst acquired humoural immunity is executed by antibodies (immunoglobulins).

Immunity – cellular immunity Immunity executed by cells belonging to the immune system (lymphocytes and professional phagocytes for specific and natural or non-specific cellular immunity, respectively).

Immunity – humoural immunity The immunity mediated by executive molecules belonging to the immune system and often found in body fluids (humours). These molecules are mostly antibodies. This type of immunity is also called antibody-mediated immunity.

Immunity – non-specific immunity This is a set of reactions at the tissue, cellular and molecular cellular level that are congenitally present in the body and whose activity is independent of prior contact with the antigen. This allows them to respond immediately after contact of the body with an infectious agent. Non-specific immunity is activated predominantly in the elimination of heterogeneous substances from tissues and in anti-infectious and antineoplastic defence.

Immunity – specific immunity It is also referred to as acquired immunity. It is the ability of the body to react against a heterogeneous antigen with a specific immunological response. Specific antibodies, executive lymphocytes and lymphocytes with an immunological memory able to react solely with the antigen that has induced their production occur in specific immunity. They do not exert action immediately after contact of the immune system with a specific antigen but instead require a latent period of several days during which the relevant clones of cells proliferate and differentiate and the production of antibodies is induced.

Immunity – transplantation immunity An acquired immunity against the cells, tissues and their antigens (major histocompatibility antigens) induced following their transfer from a genetically nonidentical donor. There can be two responses to heterogeneous histocompatibility antigens: host versus graft rejection (HvG) or graft versus host reaction (GvHR). The host versus graft rejection can be hyperacute (executed by the antibodies, e.g. in blood group differences or xenotransplantations), acute (reaction of cytotoxic T lymphocytes against heterogeneous HLA antigens) or chronic (participation of antibodies against weak histocompatibility antigens).

Immunoadherence This is the ability of professional phagocytes to adhere to their immunoadherent receptors (FcR or CR) of bacteria or other particles opsonised by antibodies or the C3b fragment of complement.

Immunoadherent receptors These are present particularly on the surface of professional phagocytes where they are involved in phagocytosis with the binding and ingestion of bacteria, immune complexes and other particles covered by antibodies or C3b, iC3b or possibly C4b fragments of complement. The particles covered by antibodies are recognised by Fc receptors, whilst particles opsonised by C3b or C4b fragments are bound to CR1 and CR3. In primates, the CR1 is present on erythrocytes and is involved in the clearance of immune complexes from the circulation.

Immunoadsorbent An insoluble substance (carrier) with a bound antigen or antibody used as a functional ligand. If the antibody is bound to the carrier, a simple separation of a specific antigen is possible or vice versa (immunoadsorbent chromatography).

Immunoassay, chemiluminescence An immunochemical method used to measure the concentration of antigen (hapten) or antibody, in which one of these reactants is labelled by a chemiluminophore (chemiluminescence).

Immunoassay, enzymatic An immunochemical method used for determining the concentration of a certain antigen (hapten) or antibody in which one of these reacting components is labelled with an enzyme. After interaction, the resultant immune complex is also labelled with this enzyme and the precise level of immune complexes can be quantified by an enzymatic reaction with a suitable, usually coloured substrate.

Immunoassay, fluorescence Fluoroimmunoanalysis is an immunochemical method for determining the concentration of antigen (hapten) or antibody in a compound mixture of different substances in which the antigen or antibody is labelled by a fluorescent agent (a fluorophore). The level of analysed substance is then measured by fluorimetry or photon absorptiometry.

Immunoassay, particle-enhanced An immunochemical method for determining the concentration of antigen (hapten) or antibody in which one of these reactants is adsorbed or chemically linked to the surface or a particle (erythrocyte, latex particles, colloid gold, etc.). Following interaction with the other reactant, agglutination or particle lysis occurs, which can be measured by various techniques.

Immunoassay, radioisotope An immunochemical method used to determine the concentration of an antigen or hapten, in which added external antigen is labelled by a radioactive isotope giving rise to the term, radioimmunoassay (RIA). Conversely, if the antibody is labelled with the radioactive isotope, the method is called an immunoradiometric assay (IRMA).

Immunoblotting A method used to detect a specific protein in a given sample of tissue homogenate or extract.

Immunocompetence A genetically determined ability of certain lymphocytes to react against an antigen with a specific immune response in a quantitative and qualitative sense. This is the ability of the body to produce a normal immune response following exposure to an antigen. When applied to lymphocytes, it means that a B or T lymphocyte is mature and can recognise antigens and is capable of mounting an immune response.

Immunodeficiency A deficiency of immunity caused by disturbances in the mechanisms of specific and/or non-specific immunity in which T cells, B cells or both types of lymphocytes, antigen-presenting cells, professional phagocytes, other accessory cells, antibodies, cytokines, complement system or other components of the immune system participate. The aetiology can be due to reduced numbers or abnormal activity of these cells, the absence, malfunction or decreased synthesis of executive and regulatory molecules of the immune system. These disturbances can involve immune system cells at different stages of development. This produces a broad range of clinical symptoms and signs, the most common of which are disturbances of anti-infectious and antineoplastic immunity. Depending on their origin, the immunodeficiency can be divided into primary (hereditary, innate), whose aetiology is a missing or defective gene or even a group of genes or secondary (acquired during development of the individual). Secondary immunodeficiency can be induced by various unfavourable physical, chemical, biological and psychosocial factors or by insufficient or improper nutrition. If the activity of the unfavourable factor wears off, secondary immunodeficiency usually normalises, in contrast to primary immunodeficiencies. A list of the most important primary immunodeficiencies is given in Table 2.
Table 2

Human primary immunodeficiencies

Primary specific immunodeficiencies

Antibody-mediated immunodeficiency

X-linked agammaglobulinemia

Selective deficiency of immunoglobulin fractions (mostly IgA)

Selective deficiency of IgG subclass

Selective deficiency of specific antibodies

Transient infantile hypogammaglobulinaemia

Common variable immunodeficiency (CVID)

Specific cell-mediated immunodeficiencies

 

 Severe combined immunodeficiency (SCID)

Adenosine deaminase deficiency (ADA)

SCID T–B (absence of T and B lymphocytes)

SCID T–B+ (absence of T lymphocytes and NK cells)

Protein kinase Jak-3 deficiency

Protein kinase ZAP-70 deficiency

 Disturbance of phagocytosis function of T lymphocytes

DiGeorge’s syndrome

Nude lymphocyte syndrome (absence of HLA class II molecules)

Failure of HLA class I molecules expression

Hyper-IgM syndrome

Chédiak–Higashi syndrome (CHS)

Omenn’s syndrome

Familial haemophagocytosing lymphohistiocytosis

Lymphoproliferative X-linked syndrome

Familial lymphoproliferative hyper-IgE autoimmunity syndrome (Job syndrome/Hyper-IgE syndrom, HIES/)

 Other antibody- and cell-mediated immunodeficiencies

Hyper-IgD syndrome

Mucocutaneous candidiasis

Ataxia-telangiectasia

Primary non-specific immunodeficiencies

Phagocytosis deficiency

 

 Disturbance of neutrophil count

Kostmann syndrome

Cyclic neutropenia

Reticular dysgenesis

Glycogenosis of IIb type

 Disturbances of phagocyte function

Chronic granulomatous disease (CGD)

LAD-syndrome I

LAD-syndrome II

Deficiency of certain lysosomal enzymes (thesaurismosis, storage diseases)

α-chain of IFN-α receptor deficiency

Deficiency of specific granules

Complement deficiency

Defects of individual components

C1-inhibitor deficiency

Disturbance of iC3b receptors (LAD-syndrome I)

Mannose binding protein (MBP) deficiency

Immunodiffusion A diffuse movement of the antigen and antibody molecule, usually in agar or agarose gel. The movement velocity depends on the concentration of both components and diffusion constants. A gel precipitate can be seen in the presence of the sought antigen or antibody at the point where they meet and their concentration is approximately equal. Under the correct conditions, it is also possible from the surface of the precipitate to determine the concentration of the evaluated component, in a similar fashion to simple radial immunodiffusion. Immunodiffusion methods are used for confirmation of diagnostically significant antigens (where a specific antibody is available) or antibodies (where a specific antigen is available).

Immunoelectrophoresis This laboratory technique is a combination of electrophoresis and immunodiffusion in agar or agarose gel. Using immunoelectrophoresis techniques, it is possible to determine the presence and amount (concentration) of antigens substantially faster than by a simple immunodiffusion method. Depending on technique, immunoelectrophoresis can be subdivided into five groups: classical immunoelectrophoresis according to Grabar and Williams (used especially for confirming multiple myeloma immunoglobulins), rocket immunoelectrophoresis, counterimmunoelectrophoresis, two-dimensional immunoelectrophoresis and immunofixation.

Immunofixation An immunoelectrophoresis method in which the separated antigens are detected directly in the gel on the basis of their precipitation with a specific antibody.

Immunofluorescence A property of certain molecules to absorb light or other form of energy and show it in the form of a photon (light with longer wavelength than that of absorbed light). It is used in immunohistochemistry and immunoassay techniques. Using the antibodies labelled by an immunofluorescent stain, it is possible to localise the applicable antigens in histological slides or study the fluorescent immune complexes through a fluorescent microscope. The same principle is also applied in sensitive fluorescent immunoassays (immunoassay, fluorescent).

Immunogenetics A branch of science representing the boundary between immunology and genetics and dealing with the genetic analysis of executive and regulatory molecules of the immune system (especially antigens of the major histocompatibility complex, immunoglobulins, cytokines and components and factors of complement) as well as the genetic regulation of immune responses.

Immunoglobulin deficiency This can be induced by abnormal function of B lymphocytes or both B and T lymphocytes. Affected individuals manifest with a low level of immunoglobulins (hypogammaglobulinaemia), abnormal function of immunoglobulins (gammopathy), hypercatabolism (excessively rapid degradation of the immunoglobulin molecules), excessive loss (upon heavy haemorrhage) or damage to lymphocytes (e.g. by drugs or lymphocytotrophic viruses). These can all lead to diseases in which the pathogenesis is a decreased immunity against most infectious agents. Subsequent severe recurrent infections are usually resistant to conventional antibiotic treatment. Primary immunoglobulin deficiencies include agammaglobulinaemia and selective deficiency of IgA or also other immunoglobulin classes and subclasses, severe combined immunodeficiency and hereditary ataxia-telangiectasia.

Immunoglobulin, normal human Intravenously applicable immunoglobulin preparation made from the blood plasma of at least 1000 healthy donors. It contains predominantly IgG and is used for substitution treatment (in deficiencies of antibody production), for prophylaxis and the treatment of certain infectious and autoimmune disorders (immunoglobulins, therapeutic preparations).

Immunoglobulin superfamily A complex of glycoprotein molecules coded for by genes with an evolutional homology, i.e. a common predecessor. The members of the immunoglobulin superfamily have several common sections of polypeptide chains in their molecules, with the same stereometric structure as the immunoglobulin chains (immunoglobulin domains). There are three types of stereometrically homologous domains identified amongst the members of the Ig superfamily: the variable (V), the constant (C) and the H domain. Currently, there are more than 40 known members of this superfamily whose basic functions are discriminative (immunoglobulins, antigenic receptors on T cells, antigens of class I and II of the major histocompatibility complex, differentiation antigens CD2, CD3, CD4, CD8 and receptors for Fc domain of immunoglobulins – FcR), adhesive (connecting) or regulatory interactions between cells. The group of adhesive molecules include ICAM-1 (CD54 – intercellular adhesion molecule-1), ICAM-2 (CD102), VCAM-1 (CD106 – vascular cell adhesion molecule) and PECAM-1 (CD31 – platelet-endothelial cell adhesion molecule). Besides the discriminative molecules, the receptor for polymeric immunoglobulins (p-IgR) and platelet-derived growth factor receptor also possess a regulatory function.

Immunoglobulins (Ig) These are glycoproteins of animal origin and include all antibodies. Their molecules consist of two identical light chains and two identical heavy polypeptide chains interconnected by disulphide bonds. The chains are spatially organised into domains (immunoglobulin domains) and modules. The first domains of the light and heavy chains are variable, whilst the others are constant. In the variable domains, the sequence of amino acids of the polypeptide chains changes amongst the antibody molecules with diverse specificity, whilst in the constant domains remains unchanged. The sections of variable domains with particularly intensive changes of amino acids in individual positions are called hypervariable sections. The hypervariable sections of the light and heavy chains are positioned in the Ig molecule side by side and form the antibody binding site, accounting for antibody-mediated specificity. There are two types of light chains (kappa and lambda). Heavy chain immunoglobulins are classified into five classes (IgA, IgD, IgE, IgG and IgM).

Immunoglobulins – chains Polypeptide chains constituting the immunoglobulin molecule. Each of the molecules contains at least two identical light (L) chains and two identical heavy (H) chains. There are two types of light chain: kappa (κ) or lambda (λ); they determine the type of immunoglobulin molecule (K or L). The heavy chains belong to five different isotypes: gamma (γ), mu (μ), alpha (α), delta (δ) and epsilon (ε); each of them determines membership to a specific immunoglobulin class. In addition to these two types of chains, the molecule of polymeric immunoglobulins (IgM and secretory IgA) also contains one joining (J) chain and the secretory IgA molecule a secretory component (SC).

Immunoglobulins – classes Isotypic variants that differ from one another by the antigenic structure of constant domains of the heavy chains of their molecules (immunoglobulins, chains). There are five known classes of immunoglobulins: IgG (having the heavy chain γ), IgM (μ), IgA (α), IgD (δ) and IgE (ε).

Immunoglobulins – effector functions All functions except those serving at the binding site. These include the ability to activate the complement, bind to the cellular Fc receptors, pass through the placenta, etc.

Immunoglobulins – genetics See Genetics of immunoglobulins.

Immunoglobulins – hypervariable regions This is the section of polypeptide chains in the variable domains where individual amino acids are able to a greater extent to change positions and thus allow immense diversity to generate millions of antigen-specific antibodies. There are six such sections in general – three on the light chain and three on the heavy chain. During the final stereometric arrangement of the immunoglobulin molecule, they become mutually close and form an antibody binding site. The hypervariable sections are also called complementary determining regions (CDR).

Immunoglobulins – idiotypes Immunoglobulin variants determined by a set of antigenic determinants, mainly in the hypervariable sections of both light and heavy chains. Such an idiotype represents the antigenicity of the antibody binding site. Some idiotypes can be found only in the organism of a certain individual (private idiotypes), whilst others can be confirmed in multiple individuals (common or cross-reacting idiotypes).

Immunoglobulins – isotypes These represent individual classes (subclasses) and types of immunoglobulins. They identify their antigenic determinants localised in the constant domains of heavy and light chains and are identical in all individuals of the given animal species. They are products of different structural genes and can be identified using xenogenic antisera (e.g. rabbit antiserum against human IgG will react with the IgG of all individuals of the human population, but not with the IgG of other biological species).

Immunoglobulins – J-chain A additional glycopeptide chain that is a component part of all polymeric immunoglobulin molecules (secretory IgA and IgM). The J (joining) chain is linked by disulphide bridges to the Fc region of immunoglobulin molecules.

Immunoglobulins – modules The highest form of stereometric arrangement of the immunoglobulin molecule. It is an aggregate arising from the mutual stereometric arrangement of the polypeptide chains of two adjacent variable or constant domains.

Immunoglobulins – molecule fragments They develop as a result of enzymatic or chemical fragmentation (cleavage) of Ig molecules. For example, the papain enzyme splits the molecule into the fragment antigen-binding (Fab) and fragment crystallisable (Fc) regions, whilst pepsin creates the F(ab,)2 and pFc, fragments. Fab contains one binding site of the original IgG molecule and F(ab,)2 two of them. Chemical degradation causes the cleavage of interchain disulphide or certain peptide bonds.

Immunoglobulins, monoclonal – see Monoclonal antibodies.

Immunoglobulins, myeloma Whole immunoglobulin molecules or their parts produced by malignant plasma cells or their precursors. They can be found in the serum of patients with multiple myeloma (monoclonal gammapathy).

Immunoglobulins – secretory component (SC) A polypeptide chain synthesised by epithelial cells to be a component of their receptor for polymeric immunoglobulins. It is a component part of the secretory IgA molecule. In IgA deficiencies, the SC binds to a secretory IgM molecule. The poly-Ig receptor and from it the resulting SC regulate the transport of these polymeric immunoglobulins to the surface of mucous membranes, where they participate in the mechanisms of local immunity.

Immunoglobulins – subclasses Immunoglobulin variants determined by the characteristic antigenic determinants on the constant domains of heavy chains. There are four known subclasses of human immunoglobulins of the IgG class (IgG1, IgG2, IgG3 and IgG4) and two subclasses of the IgA class (IgA1 and IgA2).

Immunoglobulins – therapeutic preparations These are pure immunoglobulin preparations suitable for clinical use. They are made from plasma collected from at least 1000 healthy donors. First-generation preparations (immune serum gamma globulin) can be administered only subcutaneously or intramuscularly (Subcuvia and Subgam), whilst second- and third-generation preparations (normal human immunoglobulin) can also be administered intravenously. However, they have to match safety and efficacy requirements, such as the requirement to contain pure IgG, which must not be in the form of aggregates that could induce adverse anaphylactoid reactions. The presence of IgA in intravenous preparations can induce the production of anti-IgA autoantibodies in IgA-deficient individuals and, in the event of subsequent administration, cause the reoccurrence of anaphylactoid or the occurrence of anaphylactic adverse reactions. Normal human immunoglobulin preparations such as Sandoglobulin, Flebogamma, Gammagard, Octagam and Vigam are used as substitution treatment for primary and secondary antibody-mediated immunodeficiency or can even be effective in several other disorders (Table 3). They can be administered as a prophylaxis to persons whose antibody-mediated immunity has not adequately developed at the time of definite or probable exposition to a certain contagion. These preparations contain an increased volume of antibodies, for example, against the diphtheria toxin, hepatitis B virus or rabies virus. When using immunoglobulin preparations, one has to consider not only their substituting effects but also their regulatory influence, which is why they can influence the immune homeostasis of the individual in both a positive and a negative way.
Table 3

Overview of disorders that can be effectively treated using intravenous preparations of normal human immunoglobulin

Very likely effective

Primary immunodeficiencies

X-linked agammaglobulinaemia

Common variable immunodeficiency

Selective IgG deficiency

Severe combined immunodeficiency (SCID)

Secondary immunodeficiencies

Transplant acceptors

Chronic lymphocytic leukaemia

High-risk newborns

AIDS in children

Kawasaki’s disease

Other disorders

Idiopathic thrombocytopenic purpura (acute)

Haemophilia, autoantibodies against the factor VIII

Possibly effective

Burns

Multiple myeloma

Autoimmune disorders (SLE, APS)

Juvenile rheumatoid arthritis

Myasthenia gravis

Rheumatoid arthritis

AIDS

 

Immunohormones Immunoregulatory active substances possessing the nature of hormones. They are synthesised in certain immunologically active cells and influence the development, differentiation and functional activity of other cells by acting on specific receptors. Some of them have a typical hormonal character (hormones of the thymus – thymosins), whereas others act mainly as local hormones (cytokines). The hormones are secreted in an endocrine manner and their target cells, to which a specific signal is transmitted, can be localised anywhere in the body. The secretion of local hormones is done in a paracrine or autocrine manner and their principal effect is usually limited to the neighbouring cells. Lymphocytes, however, have the ability to move around in the whole body, and so their immunoregulatory products (interleukins, lymphokines) can also have a systemic effect, despite having the character of local hormones.

Immunological tolerance A state of specific unresponsiveness (inhibition) of the immune system to a specific antigen that under normal circumstances would induce an immune response. In these circumstances, the reactivity of the lymphocyte clone capable of responding to this antigen is decreased or completely suppressed, or this clone has been eliminated from the body. The ability to respond to other antigens is preserved in an individual tolerant to a certain antigen (known as a tolerogen). Immunological tolerance has therefore the same specificity as the immunity itself. It can be either natural (spontaneous nonresponse to one’s own antigens emerging during the individual’s ontogenetic development also called ‘autotolerance’) or secondary (nonresponsiveness to extrinsic antigens). Under experimental conditions, tolerance to a specific antigen can be induced artificially.

Immunomodulation The therapeutic influence on the immune response performed for the purpose of stimulation (immunostimulation), suppression (immunosuppression) or normalisation of the immune response. Drugs normalising the immune response are those modulating a decrease or increase in the immune system activity towards normal function.

Immunomodulation therapy Treatment aimed at modulating the immune system activity of an individual. It is done either to increase the actual activity of the immune system (immunostimulation) or to suppress its activity (immunosuppression). The objective is immune normalisation, when activity of the immune system is restored to normal levels.

Immunopathology This is a subspecialisation with the application of immunological techniques in the field to the practice of pathology. It studies the pathological changes occurring as a consequence of abnormal, increased (hypersensitive) or defective (immunodeficiencies) immune responses, their aetiology and diagnosis. Immunopathological (hypersensitive) reactions are nowadays classified according to Coombs and Gell into four types:
  1. 1.

    Immediate or anaphylactic reactions (anaphylaxis) mediated in humans by the IgE class of antibodies.

     
  2. 2.

    Cytotoxic type mediated by IgG or IgM antibodies against one’s own cellular or tissue antigens; the tissue damage is caused primarily by activated complement.

     
  3. 3.

    Immune complex reactions where soluble immune complexes are formed and are deposited in various tissues and organs, such as the vascular system, the kidneys, the connective tissue or skin. Subsequently, reactive oxygen species and lysosomal enzymes are released from neutrophils leading to tissue damage mediated by the immune complex deposition.

     
  4. 4.

    Delayed-type hypersensitivity where T lymphocytes, macrophages and certain cytokines are involved.

     

Recently, a fifth type of immunopathological response has been proposed with involvement of autoantibodies against the cellular receptors. These autoantibodies can influence organ function via pathological stimulation (as agonists) or inhibition (as antagonists). Thyrotoxicosis is an example of stimulatory hypersensitivity in which the autoantibodies can falsely stimulate the TSH receptors in the thyroid, whereas in primary myxoedema (TSH-receptor blockade) or myasthenia gravis (acetylcholine receptor blockade), the autoantibodies inhibit function. The majority of autoimmune reactions belong to the second type of hypersensitivity according to this manner of classification.

Immunophilins Intracellular proteins with peptidyl-prolyl-cis-trans-isomerase activity specifically bind immunosuppressive drugs such as cyclosporine A (CyA), FK506 and rapamycin. There is a specific cytosolic immunophilin for each of them (cyclophilin for CyA), which after binding to the relevant immunosuppressant loses its enzymatic activity and thereby the ability to transmit the activation signal from the T-lymphocyte receptor to the nucleus. This is the principle of their immunosuppressant activity.

Immunopotency The ability of a certain antigen molecule to serve as an antigenic determinant, thereby inducing the production of a specific antibody.

Immunopotentiation An increase in immune system efficacy (stimulation).

Immunoprecipitation This is the production of a precipitate upon the reaction between a soluble antigen and its specific antibody. It can occur in a solution or a semisolid (gel) environment (usually in agarose gel). The technique is carried out in a qualitative or quantitative manner. Using qualitative immunoprecipitation, it is possible to determine the relationship between the amount of precipitate and the antigen–antibody concentration ratio. Huge excess of one of the two reactants can redissolve the immunoprecipitation (according to the precipitation curve or Heidelberger curve).

Immunoprophylaxis Prevention of a disease by either vaccination that induces active immunisation, or by administering an immune serum (containing specific antibodies), or by administering specific active lymphocytes, which induce passive immunity.

Immunoradiometry Immunoradiometric analysis (IRMA) by which the antibody, not the antigen, is labelled by an active radioisotope.

Immunostimulation A non-specific increase in the level of natural (innate) or specific immunity of an individual, manifested by increased rapidity and intensity of the immune response against various antigens, especially bacteria, viruses and neoplastic cells. Various immunostimulatory drugs which act on the immune system can elicit this.

Immunosuppression The suppression of the body’s immune responses by external intervention either intentionally during immunosuppressive treatment or incidentally as an adverse event (e.g. by the influence of ionising radiation or certain drugs – especially cytostatic agents, xenobiotics and bacterial toxins). Immunosuppressive treatment is used in organ (especially kidney), tissue and bone marrow transplants to prevent rejection and in the treatment of certain autoimmune disorders and other diseases with an immunopathogenesis.

Immunotherapy The treatment of abnormal immune responses by an immunostimulating or immunosuppressive agent or by biological products of either natural or recombinant origin (e.g. certain cytokines), vaccines and immune sera. It also includes desensitisation in allergic disorders.

Immunotoxicology The investigation of the toxic and adverse effects of various natural and industrial toxins, harmful substances and toxic agrochemicals (xenobiotics) in the living and working environment, as well as the adverse effects of drugs on the immune system. The immunotoxic effects of these agents can manifest itself through suppression of the immune system (immunosuppression), which leads to reduced immunity in the affected individuals against infectious and neoplastic disorders, or on the contrary, through immunopathological stimulation (immunostimulation) when an increase in the occurrence of allergic and autoimmune disorders is observed.

Immunotoxins The conjugates (complexes) of monoclonal antibodies and cytotoxic compounds can bind through a binding site of the antibody to a specific antigen of the target cell, most frequently a neoplastic cell, and so by the action of the toxic agent can kill the cell without causing injury to other cells in the body. Various vegetable or animal toxins, cytostatic agents and radionuclides can be used as the toxic component of immunotoxins. Currently, immunotoxins have only been experimentally tested in the treatment of certain tumours.

Impact of work on the onset of rheumatic diseases The doctor does not simply ask about patient’s work, he wants to know, how long the patient is sitting, standing, how long he stays outside and what type of movements he performs during work.

The load on the lumbar spine is greater when sitting compared to standing.

Static muscular work (agonistic and antagonistic muscles are stretched at the same time) is much more difficult (hairdressers, dentists and workers with stretched upper limbs) than work with dynamic muscle work (in which alternately stretch agonistic and antagonistic muscles). It’s because the permanently contracted muscle has a worse blood circulation.

Monotonous muscle work causes myalgia, tendinopathy, enthesopathy and compression syndromes, especially in beginners, as they did not acquire routine movement patterns yet.

On permanently pressurised places, periostalgia and bursitis can develop (prepatellar bursitis in parquet layers and nuns; olecranon bursitis or bursitis over the ischial tuberosity in officials).

Atypical and excessive loads may lead to the so-called stress bone fractures (fracture of spinous process of the lower section of the cervical spine typical for workers with shovel, metatarsal bone fractures in runners). Even spondylosis can in some cases be considered as a stress fracture.

Damage from vibrations can cause Raynaud’s syndrome, malacia of lunate bone and arthropathy of wrist and elbow and can lead to neuropathy. Vibrations at low frequency (e.g. vibrations of a tractor) damage lumbar discs and cause pain in the lumbar spine (Bálint et al. 1997).

Jobs may be related to certain infections (occupational exposure):
  • Veterinarians, cattle breeders – brucellosis

  • Poultry farmers or exotic birds breeders – ornitosis

  • Sewer pipes cleaners – mycoplasma, leptospirosis

  • Foresters, hunters – Lyme disease

  • Health professionals – hepatitis B, HIV

  • Certain physical effects can cause diseases of the musculoskeletal system, for example, a rapid decrease in pressure at decompression (caisson disease – decompression sickness) can cause aseptic bone necrosis.

Certain chemicals can cause disorders of the musculoskeletal system:
  • In workers in the production of PVC and in workers with organic solvent – scleroderma

  • In aluminium workers – fluorosis

  • In workers with lead (accumulator production) – gouty arthritis

Impairment A term which describes a transient or permanent decrease in the function of an organ or body when compared with the norm in the anatomic, physiological or mental sphere. These are, for example, impairments of speech and sensory organs, joint function, etc. For newer approaches, see ‘ICF classification’.

Impingement syndrome of the shoulder Narrowing of the subacromial space leads to painful friction of the affected structures as a consequence of various influences, such as trauma, microtrauma or inflammation. Typical is the so-called painful arc, i.e. pain during abduction of the shoulder from 60 to 120° when the head of the humerus has a pathologically altered subacromial space.

Impulse waves These are pneumatically generated ballistic waves with optional impulse frequency varying from 5 to 10 Hz, adjustable level of energy 1–4 bars and a power density on the impulse transmitter of 0.01–0.23 mJ/mm. It is used in the management of painful body areas. The impulse generated in the device is accelerated, thus creating the impulse wave, which penetrates the area of the body exposed to the wave. Indications of impulse waves include area application in the soft tissues, e.g. treatment of enthesopathy and tendinopathy, spatially restricted application used to influence trigger points and tender points and point application for acupuncture points.

Indications:
  • Tendon injury

  • Calcar calcanei (painful heel)

  • Dupuytren’s contracture

  • Trigger points

Incisura scapulae syndrome The suprascapular nerve is compressed in the suprascapular notch. Dull pain and tenderness to palpation is present in supraspinatous fossa. The abduction test is positive. The patient places the hand of the affected site on the contralateral shoulder, so that the elbow is in a horizontal line at the level of both shoulders. Then the patient makes a movement of the elbow towards the healthy shoulder. When the suprascapular nerve is compressed, the patient experiences a sharp pain. No changes are visible on X-ray.
  • ►Treatment

    Injections are administered locally (mesocaine + glucocorticoid) in the proximity of suprascapular notch.

Infectious arthritis: In infectious arthritis, a virulent microorganism (bacteria, fungi, viruses), which is responsible for the inflammatory process, gets into the joint.

Bacterial or septic arthritis

It is most often caused by Staphylococcus aureus, Streptococcus haemolyticus or Gram-negative bacteria, such as Pseudomonas, in children by Haemophilus influenzae and E.coli.

The infection may enter the joint either directly (intra-articular injection, injury), or through haematological route, or it may penetrate from the surrounding infected tissues or bone.

Predisposition factors are old age and immunodeficiency (inflammatory rheumatic diseases, RA, immunosuppressive treatment, HIV, drug abuse).

Signs: Very strong pain, swelling of the joint, red skin, shiver, fever and general weakness. In case of immunodeficiency of the body, the signs are much less dramatic.

Low-virulence agent may trigger chronic synovitis.

Early diagnosis is very important, since the disease may result in fatal septicaemia or severe joint destruction.

Laboratory tests: Most important is the examination of the synovial fluid, that is, microscopic examination of the swab, aerobic and anaerobic cultivation and cytological examination (cell count). If the result is negative, the test is repeated or a biopsy performed.

Radiological signs: If the case is acute, the demonstration is not typical. In chronic cases, erosion and destruction of the joint is visible. Isotope scintigraphy (Ga67 or marked white blood cells) can help confirm the diagnosis in case of joints that are difficult to access (sacroiliac and coxal joint).

Therapy: Hospitalisation at the orthopaedic or rheumatology department is inevitable.

After withdrawal of the synovial fluid, a treatment with broad-spectrum antibiotics is initiated immediately, which later, based on the result of cultivation and ATB sensitivity test, is changed to intra-articular administration, as the medication may cause irritative synovitis. ATBs are administrated intravenously for at least a week, and intramuscular administration should be avoided, if possible.

Clindamycin and cephalosporins have proved as best agents. If septic arthritis does not improve in 2–3 days, a surgical intervention with joint incision and thorough cleaning of the joint cavity is inevitable. An occasional relief joint puncture and lavage are important.

Infectious mononucleosis Also commonly known as glandular fever or Pfeiffer’s disease. It is caused by the Epstein–Barr virus (EBV), which infects B lymphocytes. It is most prevalent in adolescents and causes fever, lymphadenopathy, sore throat and fatigue, though can cause arthralgias. The Paul–Bunnell test is positive, though the monospot test looking for heterophile antibodies is now more commonly used.

Inflammation The body’s complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells or irritants. The aim of inflammation is liquidation, dilution or elimination of the injurious stimuli and damaged tissue or at least its demarcation and reparation. Based on various criteria, the inflammation can be split into protective and harming, acute and chronic, superficial and deep, etc. Four phases can be observed during the inflammatory response: vascular response, acute cellular response, chronic cellular response and healing. A number of cells that are a part of the immune system (particularly neutrophils, macrophages, T lymphocytes, endothelial cells, eosinophils, mast cells, thrombocytes), multi-enzymatic systems of blood plasma (complement, haemocoagulation system, fibrinolytic and kinin system), pro-inflammatory and anti-inflammatory cytokines, acute phase proteins, prostaglandins and other metabolites of arachidonic acid, as well as certain other mediators of inflammation, are involved in an inflammatory reaction.

A fundamental cell of acute inflammation, which reacts to its development, and which as the first cell translocated into the locus of inflammation, is the neutrophil. Macrophages and T lymphocytes are particularly involved in chronic inflammation. At the required time, these cells produce the required amount of mediators, enzymes and cytotoxins, which kill and decompose invading pathogens or damaged tissue in the course of protective inflammation. If the inflammatory stimulus still persists or if the abovementioned products are synthesised in an excessive amount, harming inflammation develops, the result of which is damage to its own cells and tissues, leading to impairment of function of various organs and systems and possibly death. Inflammatory cells can put their activities into effect only if they translocate from the circulation into the tissue where the inflammatory reaction develops. This transendothelial migration (diapedesis) of leukocytes takes place in postcapillary venules by a number of adhesive interactions between adhesive molecules on the surfaces of leukocytes and endothelium. It is a multistep process, in which selectins, integrins and immunoglobulin superfamilies, such as ICAM-1, ICAM-2, VCAM-1 and others, are involved.

Inflammatory bowel diseases – see Arthropathy in the course of inflammatory bowel diseases, Enteropathic arthritis (EA).

Infliximab (Remicade) A chimeric monoclonal antibody (consisting of murine and human components) of the IgG1 class, which binds specifically to human TNF-α. It is administered by intravenous infusions at regular intervals in doses of 3 mg/kg (rheumatoid arthritis), 5 mg/kg (ankylosing spondylitis, psoriatic arthritis or psoriasis, and Crohn’s disease) over 1 h. After the initial infusion, subsequent infusions are administered after 2 weeks, 6 weeks after the first dose, and then all subsequent doses are administered every 8 weeks. The serum concentrations of infliximab are more sustained with concomitantly administered methotrexate (MTX; a fixed oral dose of 15–25 mg/week). The co-administration of infliximab and MTX (or an alternative immunosuppressant drug if MTX is not tolerated) not only significantly suppresses the inflammatory activity of rheumatoid arthritis but also seems to improve the immunological tolerance of infliximab. The onset of action of infliximab is relatively rapid, usually seen soon after the first doses of the drug, and usually persists during the whole treatment period. However, relapse of the disease occurs in the majority of patients on withdrawal of treatment, which can be suppressed by restarting anti-TNF treatment.

Infrared radiation The invisible part of the optic spectrum, with a wavelength longer than that of visible light. It is divided into three bands according to wavelength:
  1. 1.

    Short-wave band IR-A (wavelength of 760–1400 nm), the initial radiation band

     
  2. 2.

    Middle-wave band IR-B (1400–3000 nm)

     
  3. 3.

    Long-wave band IR-C (over 3000 nm)

     

IR-A has a superficial thermal effect and penetrates to a depth of up to 1 cm; it is used for diathermy of tissue. IR-B and IR-C are used for warming-up of tissue.

Inherited complete heart block – see Neonatal lupus.

Instruments of assessing (health status measurements, outcome measurement) Questionnaires that are either completed in a controlled patient/physician interview or are self-administered by the patient. The questions are directed to obtain relevant answers as to the quality of life of the patient in relation to his/her health status. They contain items (dimensions, domains) that focus on the patient’s physical, mental and social status. Individual items or domains are scored separately. Some systems express the result as a score.

There are two main groups of instruments: generic, used in different diseases to assess the overall state of health of the patient, and condition-specific, for the given disease.

Generic instruments

MOS-SF – medical outcome study – short form 36

MOS-SF-36 8-item questionnaire with 36 questions was designed specifically for global assessment of the population health status. The questionnaire investigates the limitations in physical functions, limitations of normal daily activities caused by decreased function, limitations in social activities, body pain and mental health, limitations in normal role activities because of emotional problems, vitality and general health perceptions. The questionnaire is filled in by the patient/proband.

Nottingham health profile (Hunt et al. 1985)

There are 38 questions answered simply with yes/no. The patient/proband fills in the questionnaire alone, usually over 5–10 min. Each question is assigned a weighted value. The best score is 0; the worst is 100.

Sickness impact profile – SIP (Bergner et al. 1987)

It has six main items containing 136 questions. It monitors the level of self-attendance, mobility, ambulation, sleep, eating, work, home management, social interactions, recreation, communication, alertness and emotional behaviour. Individual items are scored and the profile is formed by summation of similar items.

Condition-specific

For rheumatoid arthritis:

Health assessment questionnaire (HAQ; Fries et al. 1982)

Originally developed for RA, it has also proved useful in osteoarthritis. It is also commonly used in many other chronic diseases. There are national versions of the questionnaire. It contains 20 items for the assessment of activities such as dressing, cleaning, rising from a chair, eating, walking, doing body care, arising and reaching for various remote items and activities outside the house. The visual analogue scale (VAS) for pain assessment is also part of it. The score from these items is averaged out and the disability index obtained. The questionnaire takes about 5 min to complete.

Arthritis impact measurement scale (AIMS; Meenan et al. 1980)

AIMS has nine items containing a total of 46 questions. Mobility, physical activity, dexterity, social sphere, household activities, activities of daily living (ADL), pain, depression and anxiety are all assessed. Subsequently other questions were added relating to the function of the upper and lower limbs and activities needed for working, leisure time utilisation and the independence of the patients. Similarly to HAQ, it is often used in RA but in contrast to HAQ time-consuming.

McMaster Toronto arthritis patient preference disability index (MACTAR; Tugwell et al. 1987)

Beside demographic questions are 25 questions related to the possibility of performing certain activities, which are assessed by three possible answers rating between no problem performing the activity, performing the activity with a little difficulty and performing the activity is impossible.

Signals of functional impairment (SOFI; Eberhardt et al. 1988)

Nine simple tasks (for the hand, the whole upper and lower extremity) performed by the patient and assessed by a physician revealing any functional limitations. They can be easily used in daily rheumatological and rehabilitation practice.

Rapid assessment of disease activity in rheumatology (RADAR; Mason et al. 1992a, b)

The patient self-assesses the course of the disease over the last 6 months. Morning stiffness is assessed in six time intervals using the VAS. According to the ARA criteria, the patient is classified to the relevant class of functional disability and assesses pain and tenderness at 10 chosen joints.

Rheumatoid arthritis disease activity index (RADAI; Stucki et al. 1995)

Besides being a model for indicating painful joints, the system contains the RADAI-5, a patient-assessed measure for disease activity in RA. RADAI-5 is a short form of RADAI with a 5-item questionnaire asking for global disease activity in the last 6 months, current disease activity with respect to tenderness and swelling of joints, arthritis pain, duration of morning stiffness and general health. RADAI-5 scores 0–10 points categorising disease activity. 0.0 up to 1.4 points correspond to a remission-like state, 1.6 up to 3.0 to mild disease activity, 3.2 up to 5.4 to moderate and from 5.6 up to 10.0 to high disease activity.

Likert’s scale for assessing joint stiffness and also psychometric data.

Overall status in rheumatoid arthritis (OSRA; Symmons et al. 1995)

Using a 3° scale (0, 1, 2), it assesses questions in four divisions (demographic data, disease activity index, impairment in the functional and social sphere and treatment in the given time). The system is valid and rapid and is undertaken by directed interview.

Rheumatoid arthritis pain scale (RAPS; Anderson 2001)

This is a valid and reliable system for assessing pain in patients with RA. It contains 24 items, each of which is evaluated on a scale from 0 to 7.

Piper fatigue scale (PFS; Piper 1990, Piper et al. 1998)

It contains 41 questions (the revised version 22 items) divided into four sections. All questions are answered using the VAS. Some of them contradict each other. The total score is evaluated.

SACRAH

Score for Assessment and quantification of Chronic Rheumatic Affections of the Hands. For ankylosing spondylitis:

Bath ankylosing spondylitis indices (BAS-indices; Calin 1995)

BASG is a global assessment tool to assess the total impact of the disease on the patient over a time interval. The patient’s assessments are made using the VAS.

BASDAI (BAS disease activity index) consists of six questions, 5 of which are related to 5 main symptoms: tiredness, pain in the spine, pain and swelling of the joints, localised regions of increased sensitivity and morning stiffness; the question assesses both the degree and duration of stiffness. All questions are measured using the VAS.

BASFI (BAS functional index) assesses responses to ten questions affecting activities of daily living using the VAS.

BASRI (BAS radiological index) has 4° of radiographic assessment of sacroileitis.

BASMI (BAS metrology index) rates measurements of rotation in the cervical spine, the distance between the tragus of the ear and the wall (Forestier fleche), both lateral deviations, Schober’s distance in a modified version and intermalleolar distance.

Dougados’ functional index (DFI) – (Dougados 1988)

It has 20 items focusing on activities of daily living and evaluated by three possible answers. The testimony of this questionnaire is more valid than metric measurement. The results are similar to those obtained by BATH-FI.

For systemic lupus erythematosus:
  • Systemic lupus erythematosus disease activity index (SLEDAI; Bombardier et al. 1992) The assessment of clinical symptoms by the severity level of the symptoms. 8 symptoms are rated with 8 points, 6 with 3 points, 7 with 2 points and 3 with 1 point.

For fibromyalgia:
  • Fibromyalgia impact questionnaire (FIG; Burckhardt et al. 1991)

This assessment consists of four items. The first item contains ten questions focusing on daily and social activities; the second one focuses on the overall well-being in the past week; the third one focuses on the possibility of work; and the fourth one focuses on how fibromyalgia problems influence the patient’s work capacity. It is evaluated using the VAS and individual items are scored.

Euro Quol questionnaire (Hurst et al. 1994)

This contains five items, each of which contains three questions. For each question, there are three possible answers. The best score is 5, the worst is 15. In addition to questions, it contains a vertical visual analogue score. It is the most widespread questionnaire for assessment of patient’s quality of life.

Oswestry low back pain disability questionnaire (Haas 1992)

It contains ten items (pain intensity, personal care, lifting, walking, sitting, standing, sleeping, social life, travelling and changing degree of pain). Each item has a choice of six answers.

For osteoarthritis:

Lequesne’s algofunctional test and assessment of the severity of hip joint impairment (Lequesne et al. 1987)

Contains the three items pain, walking and daily activities. The assessment of each item uses a severity scale from 1 to 6. The activities are rated with three points. One number expresses the function. A score of 1–4 indicates normal hip joint function; a score of 4–8 indicates moderate impairment; a score of 8–10 indicates significant impairment; and a score over 11 represents an indication for total joint replacement.

SF-SACRAH The Short Form Score for Assessment and quantification of Chronic Rheumatic Affections of the Hands. SF-SACRAH is validated for rheumatoid arthritis and for osteoarthritis of the hands. SF-SACRAH is a questionnaire with five questions dealing with function of the hand (three questions), stiffness and pain.

Western Ontario and McMaster universities osteoarthritis index (WOMAC; Bellamy 1988, 1995) This specific questionnaire is designed for assessing the function in patients with hip or knee OA. The patient him/herself answers 24 questions divided into 3 sections. Five questions deal with pain, 2 with stiffness and 17 with the activities of daily living. It is evaluated on a 5-point scale.

For psoriatic arthritis:

SASPA Stockerau Activity Score for Psoriatic Arthritis is a modified RADAI-5 questionnaire applied as a routine assessment tool for psoriatic arthritis patients. SASPA evaluates current disease activity with respect to tenderness and swelling of joints, arthritis pain, general health, duration of morning stiffness and skin symptoms.

Insulin As well as its most important role in glucose metabolism, insulin has effects on the normal development of the skeleton. It stimulates the synthesis of bone matrix and has an influence on its mineralisation. The effect on the osseous bone tissue is direct as well as mediated by IGF I.

Insulin-like growth factor (IGF) IGF-1 and IGF-2 increase the production of the collagens of bone and the synthesis of matrix and stimulate replication of the osteoblasts. In addition, IGF-I inhibits the degradation of the bone collagen.

INT Test An analytical method using iodonitrotetrazolium (INT) solution, which changes colour when incubated with leukocytes in the presence of phagocytosable particles, which is evidence of the ability to produce superoxide and other reactive oxygen intermediates (ROI). The intensity of the red colour is measured photometrically (485 nm) and is proportional to the ability of the leukocytes to kill bacteria after phagocytosis.

Integrins A family of heterodimeric glycoproteins whose molecules contain two types of polypeptide chain – α and β. They are divided into subfamilies whose members have a common β chain but different α chains. In humans, 19 α and 8 β subunits have been characterised. The subfamily of β1-integrins is referred to as very late antigens (VLA-1 to VLA-6); the subfamily of β2-integrins is composed of leukocyte adhesins and has three very well characterised members: LFA-1 (CD11a/CD18), CR3 (CD11b/CD18) and CR4 (CD11c/CD18), whilst the cytoadhesins of the β3-integrin subfamily represent the receptors for vitronectin. Integrins are surface adhesion molecules responsible for tissue coherence, for cellular interactions during embryonic development and for immune responses, including the binding of cells to molecules of the extracellular matrix, including collagens and fibronectin. They play a major role in the colonisation of lymphoid tissues and organs by lymphocytes and other immune system cells, in the migration of leukocytes from the microcirculation to the tissues during inflammation (diapedesis) and in the interaction of lymphocytes with antigen-presenting cells.

The dominant osteoclastic integrin αvβ3 is a member of αv family of integrins. It is expressed on osteoclasts following activation with RANKL and is an essential part of physiological bone resorption. The competitive ligands for αvβ3 are able to slow down the osteoresorption and are candidates for antiresorptive treatment of bones.

Intercellular adhesion molecule (ICAM) At present, there are four types known – ICAM-1, ICAM-2, ICAM-3 and ICAM-4 – all belonging structurally to the immunoglobulin superfamily. ICAM-1 (CD54) is a membrane glycoprotein found on various cells, including endothelial and dendritic cells. ICAM-1 binds specifically to the β2-integrin receptor LFA-1, thereby helping to perform various interactions between T lymphocytes and antigen-presenting cells (immune response initiation), between neutrophils and cells of the vascular endothelium (initiation of the inflammatory reaction) or between other pairs of cells. IFN-γ, TNF-α and IL-1 stimulate its production. ICAM-2 (CD102) and ICAM-3 have similar properties to ICAM-1. Apart from LFA-1, they can also bind to the complement receptors CR3 and CR4.

Intercellular substance of cartilage matrix Basically an amorphous gel consisting mostly of proteoglycans, but also containing proteins and glycoproteins. This gel is reinforced by a fine, strong network of type II collagen with small amounts of type VI, IX and XI collagens. Amongst glycoproteins, the matrix contains chondronectin and chondrocalcin.

Approximately half of the organic matter of the matrix consists of viscous hydrophilic proteoglycans. The presence of large macromolecular arrangements of glycoproteins, which provide a molecular substrate for the considerable elasticity (resilience) of the cartilage, is a typical attribute of the matrix. Molecules of proteoglycans form the skeleton in which molecules of interstitial fluid and ions are present. Certain molecules of interstitial fluid even bind through hydrogen bridges to negatively charged units in the glycosaminoglycan chains of proteoglycans. Enormous cartilage-specific proteoglycan is denoted as aggrecan. Its molecules are immobilised in the skeleton of collagen fibrils. Approximately 100 chains of chondroitin sulphate and 30 chains of keratan sulphate are bound to the protein nucleus of aggrecan. Aggrecan belongs to the group of hyaluronan-binding proteins. The bond between aggrecan and hyaluronan is stabilised by a protein called link protein. Negative charge and high osmotic pressure are formed in the skeleton of proteoglycans as each molecule of aggrecan contains amounts of sulfone groups. It is the reason that the cartilage tends to seal up. The sealing up is controlled by the skeleton of collagen fibrils, which are permanently stretched, even in uncharged cartilage. Charged cartilage reacts by a change of osmotic and hydrostatic pressure and interstitial fluid moves from charged to uncharged areas of the cartilage, whilst aggrecan remains bound to hyaluronan and immobilised in the collagen skeleton.

Integrins A family of small cytokines more commonly referred to as chemokines.

Interferential currents (IC)

The application of two medium-frequency currents that easily overcome skin resistance. An effective low-frequency current develops in the depth of the affected tissue after their interference, and its size is determined by the difference between the frequencies of both alternate currents. Modulations used:
  • Constant 0–10 Hz: used for muscle gymnastics

  • Constant 90–100 Hz: has a sedative and spasmolytic effect

  • Constant 100 Hz: spasmolytic effect

  • Rhythmic 0–10 Hz: for muscle gymnastics

  • Rhythmic 50–100 Hz: has an analgesic and spasmolytic effect and causes hyperaemia

  • Rhythmic 90–100 Hz: has an analgesic and spasmolytic effect

  • Rhythmic 0–100 Hz: has an alternating suppressive and irritating effect; used in pathologically altered cellular functions (oedema)

Interferon alpha (IFN-α) The main type of interferon produced by leucocytes. It is induced by foreign cells, cells infected by a virus, neoplastic cells and bacteria. It has about 15 isotypes whose genes are localised on chromosome 9 in man. Recombinant IFN-α (Intron-A, Roferon-A) is used in the treatment of hairy-cell leukaemia, chronic myeloid leukaemia, Kaposi sarcoma, malignant melanoma, multiple myeloma, chronic hepatitis B and C and several other disorders.

Interferon beta (IFN-β) It is produced mainly by fibroblasts with nucleic acids of viral or other origins serving as its inductors. Its gene is also localised on chromosome 9. Recombinant IFN-β (Betaferon) is used in the treatment of relapsing multiple sclerosis. IFN-α and IFN-β have antiviral and antiproliferative effects, and to a lesser extent immunoregulatory effects.

Interferon gamma (IFN-γ) A product of activated T-helper (TH1) and T-cytotoxic (TC) lymphocytes or NK cells synthesised by them in response to a specific antigen or mitogens. It is therefore considered a typical lymphokine whose gene is localised on chromosome 12. Its main function is immunoregulatory, but it does have antiviral and antiproliferative effects as well. It is able to activate many different genes allowing activation of macrophages, giving them the ability to kill intracellular bacteria, to lyse neoplastic cells and to express HLA class II antigens on their surface. It also stimulates the expression of HLA class I antigens on different cells, thereby making them more sensitive to the activity of cytotoxic T lymphocytes. It facilitates the differentiation of B and T lymphocytes. Recombinant IFN-γ (Actimmune) is used for the prevention and treatment of the chronic granulomatous disease and certain viral disorders. IFN-α and IFN-β exert their activity via the same receptor, whilst IFN-γ has a unique receptor.

Interferon omega (IFN-ω) Originally referred to as IFN-α2. It has similar properties to IFN-α.

Interferons Classed amongst the cytokines. In mammals, there are five known types of interferons (IFN) which are divided into two classes. IFN-α, IFN-β, IFN-ω and IFN-τ belong to the first class, whilst the second class is represented by IFN-γ.

Interleukin 1 (IL-1) A glycoprotein with MW 17KDa. It exists in two forms – IL-1α and IL-1β – which are coded for by separate genes on chromosome 2. They act via a common receptor (IL-1R), which is found on different types of cells. The biological effects of IL-1 are therefore pleiotropic. IL-1α and IL-1β are typical pro-inflammatory cytokines synthesised by macrophages, monocytes and dendritic cells involved in the immune responses, inflammatory processes and haematopoiesis. They stimulate the proliferation of B and T lymphocytes and cause the expression of receptors for IL-2, leukoadhesive molecules on neutrophils and endothelial cells, the chemotaxy of neutrophils, macrophages and lymphocytes and the cytotoxic activity of NK cells. Further actions include the proliferation and synthesis of collagen by epithelial cells and fibroblasts, the synthesis of prostaglandins in macrophages and in the hypothalamus and the synthesis of acute phase proteins in hepatocytes. It participates in the majority of overreactive and pathological immune reactions. It exerts a damaging effect in rheumatoid arthritis and chronic inflammatory bowel diseases (ulcerative colitis, Crohn’s disease). This harmful effect can be therapeutically blocked by monoclonal antibodies against IL-1 or by the natural antagonist of its receptor (IL-1RA).

Interleukin 2 (IL-2) A glycoprotein with MW 15.5KDa coded for by a gene localised on human chromosome 4. It acts via its receptor IL-2R, which can have low-affinity, medium-affinity or high-affinity forms. It is produced by TH1-lymphocytes after their activation with an antigen and IL-1. IL-2 is a growth factor for T and B lymphocytes and an activating factor of TC lymphocytes and NK cells. In TH lymphocytes, it stimulates the production of other cytokines such as IL-4 and IFN-γ as well as the antineoplastic activity of LAK cells. Sufficient production of IL-2 and expression of IL-2R is of crucial importance for adequate T-cell immunity. A decreased production of IL-2 is observed in patients with severe combined immunodeficiency, Nezelof’s syndrome, AIDS, type I diabetes mellitus and systemic lupus erythematosus. The stimulation of LAK cells has gained ground in the treatment of certain neoplasms.

Interleukin 3 (IL-3) A glycoprotein with MW 20KDa secreted mainly by TH1- and TH2-lymphocytes, NK cells and mast cells. Its gene is localised on chromosome 5 in the proximity of the gene for GM-CSF. In the past, it was referred to as a multipotent colony-stimulating factor (multi-CSF, colony-stimulating growth factors). It acts via a common receptor for IL-3 and GM-CSF. It is a growth factor of haematopoietic stem cells, megakaryocytes, erythrocytes, granulocytes, mast cells and macrophages.

Interleukin 4 (IL-4) It is produced mainly by TH2-lymphocytes, but also by mast cells and basophils. It is coded for by a gene localised on human chromosome 5. It stimulates the proliferation of early B cells inducing their differentiation and production of IgM, IgG1 and IgE. Furthermore, IL-4 stimulates the proliferation of T lymphocytes, the production of antigen-specific cytotoxic T cells and the expression of HLA antigens and is an activating factor of macrophages and a growth factor of mast cells. With its capability to switch antibody production from IgM to IgE, it can greatly influence the development of the immediate type of allergic reactions which are mediated by IgE antibodies. It has an anti-inflammatory effect.

Interleukin 5 (IL-5) Secreted mainly by TH2-lymphocytes and activated mast cells. Its gene is localised on chromosome 5. Its most important pleiotropic effects include the activation and stimulation of B cell and eosinophil proliferation, stimulation of cytotoxic T lymphocytes and the capability of switching between the production of IgM antibody isotype to IgA antibody isotype and the ability to increase the expression of receptors for IL-2. During these activities, it has a synergic action, especially with IL-2 and IL-4. Together with IL-3 and GM-CSF it controls the development of eosinophils.

Interleukin 6 (IL-6) A glycoprotein whose gene is localised on chromosome 7. Originally it was termed IFN-β2. It is synthesised by various cells including TH2- and B lymphocytes, macrophages, endothelial cells, fibroblasts, mast cells and a number of neoplastic cell lines. It is considered a typical pro-inflammatory cytokine. Its production is also induced by a number of other cytokines (IL-1, IL-2, TNF-α, IFN-γ, etc.). It acts as an endogenous pyrogen and an activator of synthesis of acute phase proteins in hepatocytes, as well as a final growth factor for the differentiation of the B cell to plasma cells, and as growth factors of plasmocytomas and myelomas. Increased IL-6 synthesis is observed in a number of disorders, such as rheumatoid arthritis, systemic lupus erythematosus, AIDS, other infections, a number of neoplasms and in acute transplant rejection.

Interleukin 7 (IL-7) It facilitates the differentiation of lymphoid stem cells into early precursor B and T cells and acts as a growth factor of T lymphocytes. It is synthesised by stromal cells of the bone marrow and thymus. It activates macrophages and stimulates the proliferation of thymocytes. It acts via high-affinity receptors belonging to the haematopoietin receptor superfamily.

Interleukin 8 (IL-8) It belongs to chemokines and was originally called neutrophil-activating peptide-1 (NAP-1). Its gene is localised on human chromosome 4 and codes for a small protein containing only 79 amino acid units (MW 8.4KDa). It is produced mainly by monocytes, macrophages and endothelial cells during a response to various factors inducing an inflammatory reaction. It acts via a specific receptor that can be found only on neutrophils, and so IL-8 is their crucial chemotactic and activating cytokine. In addition, it also induces the expression of β2-integrins on neutrophils, which is of crucial importance for their transendothelial migration to the focus of inflammation. Its effect is hypothesised in pathological reactions involving the neutrophils, such as in adult respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis or the late phase of bronchial asthma.

Interleukin 9 (IL-9) It acts predominantly as a helping, co-stimulatory factor of other cytokines during the development of haematopoietic cells. It thus potentiates the proliferation of certain clones of T-helper cells, foetal thymocytes in the presence of IL-2, mast cells after their induction by IL-3 and erythrocytes in cooperation with erythropoietin. It is produced mainly by TH2-lymphocytes under the influence of IL-1. Its gene is localised on chromosome 5 together with the genes coding for IL-3, IL-4, IL-5 and GM-CSF. The deletion of this chromosomal section is linked to the occurrence of malignancies (myelodysplastic syndrome, acute non-lymphocytic leukaemia).

Interleukin 10 (IL-10) It is produced mainly by TH2-lymphocytes and to a lesser extent by TH0-lymphocytes, monocytes, macrophages and activated B lymphocytes. It is a pure protein (contains no saccharides) with a MW 18KDa. It inhibits the production of other cytokines (IFN-γ, TNF-β, IL-2 and IL-3) by TH1-lymphocytes, cytotoxic T lymphocytes and NK cells. It inhibits the synthesis of pro-inflammatory cytokines IL-1, IL-6, IL-8, GM-CSF and TNF-α in macrophages. It blocks the presentation of proteinous antigens. It acts as a natural immunosuppressive and anti-inflammatory agent. Therefore, it is of possible clinical use in chronic inflammatory conditions and autoimmune disorders.

Interleukin 11 (IL-11) It has multiple biological properties similar to IL-6. Both these cytokines, however, have separate receptors. IL-11 particularly controls the lymphopoietic and haematopoietic systems, hepatic cells and adipogenesis. It is a growth factor of megakaryocytes and, together with IL-3, participates in the development of thrombocytes. It stimulates B lymphocytes during the antibody-mediated response to T-independent antigens. It is produced by the supporting fibrous tissue in bone marrow and by fibroblasts. Its gene is localised on chromosome 5. It facilitates the development of plasmocytoma, which indicates its role in tumour production.

Interleukin 12 (IL-12) Its molecule consists of a heterodimer of two glycoprotein chains linked together by disulphide bonds. The genes for both chains in a human are localised on different chromosomes. The gene coding for the polypeptide chain p35 is localised on chromosome 3 and a gene coding for p40 is localised on chromosome 5. The principal producers of IL-12 are monocytes and macrophages. It is an activation factor of NK cells, stimulating their cytotoxicity in the ADCC reaction (antibody-dependent cell cytotoxicity), and increasing the expression of the CD56 molecule which is their typical surface marker. By its activity, NK cells develop into the more effective LAK cells. In this activity, it resembles IL-2, but with a lower effect (about 50 %). In addition, IL-12 facilitates the occurrence of specific human cytotoxic T lymphocytes against certain neoplasms, stimulates the proliferation of TH and TC cells and inhibits the secretion of IgE stimulated by IL-4. It is considered to be the principal stimulator of IFN-γ production by TH1-lymphocytes. In this sense, it acts in synergy with IL-18. With respect to these immunoregulatory influences, IL-12 has been studied in the treatment of parasitic and neoplastic disorders with the advantage of low toxicity and minimal adverse events.

Interleukin 13 (IL-13) An anti-inflammatory cytokine whose gene is localised on chromosome 5 in close proximity to the gene coding for IL-4. It has similar biological effects as the IL-4. It is produced predominantly by activated TH2-lymphocytes. It exerts a regulatory activity on various immune system cells, especially monocytes, macrophages, B lymphocytes and NK cells. It is a chemotactic factor for monocytes and macrophages but inhibits the production of pro-inflammatory cytokines in them. It therefore can be regarded as a significant endogenous anti-inflammatory regulator, similar to IL-10. It inhibits the replication of HIV-1 in macrophages and monocytes, so differs from IL-3 and GM-CSF, which, on the contrary, stimulate the replication of this etiological agent of AIDS. It also stimulates the proliferation and differentiation of B lymphocytes, similar to IL-4.

Interleukin 14 (IL-14) A glycoprotein with MW 55KDa which previously was termed a high-molecular B-cell growth factor. It is secreted mainly by follicular dendritic cells, T cells of the germinal centres and certain neoplastic cells. Its main function is to increase B-cell proliferation and to induce and maintain the production of memory B cells. The receptor for IL-14 can be found only on activated B lymphocytes, not on resting ones. The IL-14 molecule has a similar amino acid sequence as the Bb factor, present in the alternative pathway of complement activation.

Interleukin 15 (IL-15) A glycoprotein with MW 15KDa and the function of a pro-inflammatory cytokine. It is produced by multiple cells and tissues, including activated macrophages, fibroblasts, skeletal muscles and the kidneys. It increases the cytotoxicity of CTL (cytotoxic T lymphocytes) and NK cells. In this way, it is similar to IL-2 and IL-12. It binds to a receptor consisting of three polypeptide chains, two of which are identical to the receptor for IL-2. IL-15 induces proliferation of the mast cells and helper and cytotoxic lymphocytes, including those having the antigen receptor gamma/delta. It stimulates the production of IL-5 by allergen-specific T-cell clones, thereby moving the TH1/TH2 balance to favour TH2-cells, with associated participation in allergic responses mediated by this T-lymphocyte subpopulation. IL-15 is an effective chemotaxin of T lymphocytes; it suppresses their apoptosis and induces the expression of ligands for leukoadhesive β-integrins. It is hypothesised that it plays a key role in the upkeep of chronic inflammation in diseases such as rheumatoid arthritis, pulmonary sarcoidosis, bronchial asthma and ulcerative colitis.

Interleukin 16 (IL-16) An immunomodulatory and pro-inflammatory cytokine whose structure is much conserved amongst individual animal species. It is synthesised by cytotoxic (CD8+) lymphocytes in the form of a high-molecular precursor (MW 80 kDa), whereby polypeptide chains with a MW 14 kDa emerge in the producing cells. These chains polymerise to tetrameres which are the only biologically effective form of IL-16. They are secreted by CD8+ lymphocytes in the response to an antigen, mitogen, histamine or serotonin. IL-16 uses the CD4+ molecule as a receptor, which is why it exerts its action not only on the helper T lymphocytes but also on macrophages and eosinophils which also have this differentiation antigen on their surface. IL-16 is a chemotactic factor for these cells, and it induces in them the synthesis of other cytokines and also the expression of HLA-DR histocompatibility antigens. On the other hand, after binding to CD4+ lymphocytes, IL-16 inhibits the ensuing immune response as well as the infectiousness and intracellular replication of HIV-1, the aetiological agent of AIDS. The epithelial cells of the airways of patients with asthma can also release a biologically effective IL-16, whilst the epithelial cells of healthy individuals cannot. This suggests a potential therapeutic effect for IL-16 inhibitors.

Interleukin 17 (IL-17) A glycoprotein containing 155 amino acid units that has been described as recently as 1995. Its amino acid sequence shows a considerable homology with one of the proteins of herpetic lymphotropic virus (HVS13). It is produced as a dimer by activated T lymphocytes. It stimulates fibroblasts, endothelial and epithelial cells to synthesise IL-6, IL-8 and GM-CSF, which indicates that it could contribute to inflammatory processes involving T lymphocytes.

Interleukin 18 (IL-18) A pro-inflammatory cytokine which was originally described in 1989 as an inducing factor of IFN-γ (IGIF). However, this activity is performed in conjunction with a secondary stimulus such as IL-12, mitogens or a microbial agent. Both cytokines (IL-18 and IL-12) act in synergy and have a critical role in inducing the production of IFN-γ especially by TH1-lymphocytes. IL-18 is produced predominantly by activated macrophages in the form of an active precursor that is cleaved by caspase 1 (formerly this protease was referred to as IL-1β enzyme converting – ICE) to the active cytokine. IL-18 is structurally similar to IL-1β and is coded for by a gene localised on chromosome 9. It acts mainly via a specific receptor, IL-18R, whose soluble form (sIL-18R) is able to neutralise the effects of IL-18. The most significant pro-inflammatory activity of IL-18 is its capability to induce the production of TNF-α, IL-1β, GM-CSF, chemokines CXC and CC, Fas ligands and the nuclear factor κB (NF-κB). The stimulation of Fas ligand expression on NK cells and T lymphocytes then leads to an increase in their cytotoxic activity. On the other hand, IL-18 is a very effective activator of HIV-1 (aetiological agent of AIDS) replication in human macrophages. The normal concentration of IL-18 in the blood is 50–150 pg/ml, whereas in patients with acute lymphoblastic leukaemia, chronic lymphocytic leukaemia and acute and chronic myeloid leukaemias, it rises to 200–1200 pg/ml. The overproduction of IL-18 leads to an increased production of nitric oxide (NO), which then participates instantly in various pathological reactions.

Interleukin-19 (IL-19) It was described in 1998. It is found on 1st chromosome near gene for IL-10, and it has similar chemical structure. It is assumed that his recombinant form will be effective as anti-inflammatory drug (it lowers level of interferon gamma, TNF and IL-6).

Interleukin-20 (IL-20) It consists of 183 amino acid units coded by gene on 12th chromosome. It belongs to pro-inflammatory cytokines, because it stimulates synthesis of various proteins of acute inflammatory phases.

Interleukin-21 It was described in 2000. It is coded by gene on human 4q26-q27 chromosome as precursor consisting of 162 amino acid units. After its processing, a biologically active polypeptide is created with Mr 15,000 consisting of 131 amino acid units. It has significant homology with IL-2, IL-4 and mainly with IL-15. It is produced probably by activated peripheral T lymphocytes.

Interleukin-22 (IL-22) It was described in 2000. It is similar to IL-10. It is produced by active T lymphocytes. On contrary to IL-10, it is not able to do inhibition of pro-inflammatory cytokines in monocytes after stimulation of polysaccharides. On the other hand, it has inhibition effect on production of IL-4 lymphocytes Th2.

Interleukin-23 (IL-23) It was described in 2000. It is created by activated dendritic cells. Human IL-23 stimulates production of IFN-gamma and proliferation of T lymphocyte induced by phytohemagglutinin, same as proliferation of CD45RO memory cells.

Interleukin-24 (IL-24) Member of IL-10 family. It was originally described as melanocyte differential factor (mda-7). It induces apoptosis of various types of carcinoma cells.

Interleukin-25 (IL-25) Member of IL-17 family. It is produced by Th2 cells. It stimulates production of further cytokines typical for this subpopulation of helper T lymphocytes, mainly IL-4, IL-5 and IL-13. These cytokines intensively increase levels of serum IgE, IgG1 and IgA, inducing increased production of eotaxin in lungs and eosinophilic blood cells and pathological changes in lungs, gastrointestinal tract and eosinophilic infiltrate, increased production of mucus and hyperplasion of epithelial cells. Its properties can increase allergic inflammatory answer.

Interleukin-26 (IL-26) This cytokine is a member of family IL-10. It is produced by memory cells, and it participates on transformation of phenotype of human T lymphocytes after infection by herpetic virus.

Interleukin-27 (IL-27) Early product of activated cells presenting antigen.

Interleukin-28 (IL-28) It was described together with IL-29 in 2003. IL-28 and IL-29 have partial homology with interferons and family IL-10. Both interleukins have antiviral activity and they belong to IFN-III.

Interleukin-29 (IL-29) – see IL-28.

Interleukin-30 (IL-30) New name for subunit p28 of interleukin IL-27.

Interleukin-31 (IL-31) It is produced mainly by Th2-lymphocytes. Overexpression of IL-31 in mice induces phenotype with severe pruritus, alopecia and impairment of skin similar as in atopic dermatitis. It is assumed that IL-31 participates in skin allergic illness.

Interleukin-32 (IL-32) It exists in four variants producing human peripheral lymphocytes, NK cells and epithelial cells; it is assumed that it takes part in inflammatory and autoimmune process.

Interleukin-33 (IL-33) It is produced by various cells, and it belongs to group of cytokine family with IL-1. It binds to specific receptor present on lymphocyte Th2.

Interleukin-35 (IL-35) It is part of cytokine family familiar with IL-12. It was found in high concentration in trophoblast, probably could have some part in foetus tolerancy by mother.

Interleukins Cytokines participating in the regulatory interactions between leukocytes. There are currently 33 known interleukins, which are termed by abbreviations IL-1 to IL-33.

Intermittent hydrarthrosis of the joints (hydrops articulorum intermittens) Characterised by recurrent attacks of a predominantly unilateral and relatively painless, non-inflammatory joint effusion. It is a long-lasting disorder often with life-long persistence. The knee joint is the most frequently affected joint, though rarely it can affect the elbow, hip or shoulder joints.
  • ► Clinical symptoms and signs

    Periodic recurrent joint effusion

    No apparent radiologic joint damage

    Very rarely progresses to rheumatoid arthritis

International classification of functioning (ICF) This has replaced the previous IDH classification (impairment–disability–handicap). In 2001, the ICF (international classification of functioning) was issued by the World Health Organisation as an international framework for measuring health and disability at both individual and population levels. It was endorsed by all 191 Member States of the World Health Organisation. The ICF classification replaced the term ‘disability’ by ‘activity’, whilst a number designate ‘diminished activity’. In place of ‘handicap’, it uses the term ‘participation’ (in social life). A number also designate ‘restricted participation’. In the ICF classification, ‘environment’ is a new dimension, where facilitating ‘F’ and barrier ‘B’ factors are also included.

Intra-articular glucocorticoid treatment The intra-articular injection of glucocorticoids is a useful method for suppressing active synovitis within a joint. Intra-articular injections should not be used too frequently or to the joints without signs of actual inflammation. One joint should not be treated more than 3–4 times in a year. Most frequently triamcinolone acetonide (Kenalog) and methylprednisolone (Depo-Medrone) are used, though hydrocortisone can be used if only a short-term effect is required.

Intra-articular treatment Rheumatoid arthritis in adults and adolescents is probably the disorder in which most intra-articular injections are given by rheumatologists. They are particularly useful when exceptional inflammatory activity is present in one or more joints. They are also used following disease flare to cover the delayed effect of an increase in general systemic treatment (DMARD’s). In children with juvenile idiopathic arthritis, the choice of preparations is limited (methylprednisolone is more appropriate) due to potential growth disturbance of the affected joint. The dosing interval between intra-articular injections into the same joint should generally not be less than 3 months.

Potential hazards of intra-articular and intralesional injections of glucocorticoids:
  • Radiological deterioration of the joints – steroid arthropathy (Charcot-like arthropathy, osteonecrosis – low incidence)

  • Iatrogenic infection – very rare complication

  • Rupture of the tendons

  • Tissue atrophy, adipose necrosis, calcifications

  • Nerve damage (most frequent after carpal tunnel injection)

  • Post-injection flare

  • Uterine bleeding

  • Pancreatitis – rarely

  • Erythema and sensation of warmth on the face and body

  • Posterior subcapsular cataract (only after many injections)

Iontophoresis This is a noninvasive method of inserting treatments into the body using a galvanic current. Histamine (muscle relaxant effect), novocaine, lidocaine, dionine (analgesic effect), hyaluronidase (fibrolytic effect) and hydrocortisone (anti-inflammatory effect) are inserted from the anode. Salicylates (anti-inflammatory and fibrolytic effect) and iodine (fibrolytic effect) are inserted from the cathode. When using nonsteroidal anti-inflammatory drugs, the active electrode can vary.

Ir genes (immune response genes) An obsolete term for genes regulating the immune response of an individual to specific antigens, both in a quantitative and qualitative sense (immune response genes). The current view is that these genes are now the class II MHC (major histocompatibility complex) genes.

Isolated vasculitis of the central nervous system (CNS) A rare disorder occurring in middle age. Headache, nausea and vomiting are the most prominent clinical features. Confusion, dementia and loss of consciousness together with signs of focal ischemic cerebral event (stroke) can also be seen. The diagnosis is confirmed using cerebral angiography or a targeted biopsy of the CNS. Aggressive treatment with corticosteroids and cyclophosphamide can reduce the mortality of this, often fatal, disorder.

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Jozef Rovenský
    • 1
  • Juraj Payer
    • 2
  • Manfred Herold
    • 3
  1. 1.National Institute for Rheumatic DiseasesPiestanySlovakia
  2. 2.Fifth Department of Internal MedicineComenius University University HospitalBratislavaSlovakia
  3. 3.Department of Internal Medicine VIMedical University of InnsbruckInnsbruckAustria

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