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Autoinflammation and Autoimmunity

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Abstract

The elucidation of the genetic basis for hereditary recurrent fever syndromes validated the role of innate immune dysregulation in diseases formerly viewed as autoimmune. Recognizing the non-autoimmune nature of tumor necrosis factor receptor-associated periodic syndrome (TRAPS), one such syndrome, and the lack of evidence for autoantibodies or B- or T-cell involvement in the context of the emergent genetics, led to the proposal of the term autoinflammation in 1999. While formally coining a new term for this type of inflammation against self, the definition was essentially stating what inflammation was not, rather than what it was. Based on the lack of an association with humoral or cellular mediated immunity and the propensity for recurrent seemingly unprovoked attacks of inflammation, fevers, elevation of inflammatory markers, without high-titer autoantibodies or antigen-specific T lymphocytes, the new designation of autoinflammatory disorders also included some conditions that would have previously been considered autoimmune, e.g. Behçet disease (BD). BD is a prime example of the two-tiered classification of inflammation against self since BD has a strong population level human leukocyte antigen (HLA)-B51 association. Given the classically defined role of major histocompatibility complex (MHC)-I molecules in peptide presentation to T cells, this incriminates adaptive immunity in BD immunopathology, which was supported by clinical therapeutics, where immunosuppressant agents like azathioprine had a proven role in disease management. The purpose of this chapter is to summarize the overlap and differences between autoinflammatory and autoimmune disorders.

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Abbreviations

AAV:

ANCA-associated vasculitis

ACPA:

Anti-citrullinated protein antibodies

ALPS:

Autoimmune lymphoproliferative syndrome

AOSD:

Adult-onset Still disease

APECED:

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

ATD:

Autoimmune thyroid disorder

BD:

Behçet disease

CAPS:

Cryopyrin-associated periodic syndromes

CARD:

Caspase activation and recruitment domains

CMML:

Chronic myelomonocytic leukaemia

DITRA:

Deficiency of IL-36 receptor antagonist

DM:

Dermatomyositis

DMARD:

Disease modifying anti-rheumatic drugs

ERAP-1:

Endoplasmic reticulum aminopeptidase 1

FMF:

Familial Mediterranean fever

GCA:

Giant cell arteritis

GWAS:

Genome-wide association studies

HIDS:

Hyperimmunoglobulinemia D syndrome

HLA:

Human leukocyte antigen

IBD:

Inflammatory bowel disease

IFN:

Interferon

IL:

Interleukin

IPEX:

Immune dysregulation polyendocrinopathy enteropathy x-linked syndrome

MAS:

Macrophage activation syndrome

MDS:

Myelodysplastic syndrome (MDS)

MHC:

Major histocompatibility complex

MKD:

Mevalonate kinase deficiency

NADPH:

Reduced nicotinamide adenine dinucleotide phosphate

NF-ĸB:

Nuclear factor kappa B

NLR:

Nucleotide-binding oligomerization domain-like receptors

NOD:

Nucleotide-binding oligomerization domain

PAAND:

Pyrin-associated autoinflammation with neutrophilic dermatosis

PAPA:

Pyogenic arthritis pyoderma gangrenosum and acne syndrome

PBS:

Primary biliary cirrhosis

PM:

Polymyositis

PsA:

Psoriatic arthritis

RA:

Rheumatoid arthritis

RAEB:

Refractory anemia with excess blasts

RCMD:

Refractory cytopenia with multilineage dysplasia

SJIA:

Systemic juvenile idiopathic arthritis

SLE:

Systemic lupus erythematosus

SNP:

Single nucleotide polymorphism

SNS:

Self/non-self

SpA:

Spondyloarthropathies

SSc:

Systemic sclerosis

STAT:

Signal transducer and activator of transcription

T1DM:

Type 1 diabetes mellitus

TLR:

Toll-like receptor

TNF:

Tumor necrosis factor

TNFR:

Tumor necrosis factor receptor

TRAPS:

Tumor necrosis factor receptor-associated periodic syndrome

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Authors and Affiliations

  1. NIHR Leeds Musculoskeletal Biomedical Research Unit, Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, Chapel Allerton Hospital, University of Leeds, Leeds, UK

    Dennis McGonagle & Abdulla Watad

  2. Department of Medicine ‘B’, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Israel

    Abdulla Watad

  3. Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel

    Abdulla Watad

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  1. Dennis McGonagle
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  2. Abdulla Watad
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Correspondence to Dennis McGonagle .

Editor information

Editors and Affiliations

  1. Pediatric Rheumatology Unit, Shaare Zedek Medical Center and Hebrew University, Jerusalem, Israel

    Philip J. Hashkes

  2. Department Paediatrics, Division of Rheumatology, The Hospital for Sick Children and University of Toronto, Toronto, ON, Canada

    Ronald M. Laxer

  3. Department of Internal Medicine, Radboudumc Expertisecenter for Immunodeficiency and Autoinflammation, Radboud University Medical Center, Nijmegen, The Netherlands

    Anna Simon

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McGonagle, D., Watad, A. (2019). Autoinflammation and Autoimmunity. In: Hashkes, P., Laxer, R., Simon, A. (eds) Textbook of Autoinflammation. Springer, Cham. https://doi.org/10.1007/978-3-319-98605-0_38

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  • DOI: https://doi.org/10.1007/978-3-319-98605-0_38

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