Abstract
Complement is part of the innate immune system and underlies one of the main effector mechanisms of antibody-mediated immunity. Among its physiological activities, complement mediates the disposal of immune complexes and the products of inflammatory injury. Accordingly, low levels of complement suggesting ongoing complement activation and consumption are a well-known phenomenon in patients with cryoglobulinemia. The consumption of complement components in serum is paralleled by the deposition of complement in affected tissues such as the kidney. Experimental data suggest that complement activation is a major factor explaining the inflammatory organ damage seen in cryoglobulinemia in vivo. However, more studies are required to clarify the pathogenic role of complement in cryoglobulinemia.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Fujita T (2002) Evolution of the lectin-complement pathway and its role in innate immunity. Nat Rev Immunol 2:346–353
Zipfel PF, Skerka C (2009) Complement regulators and inhibitory proteins. Nat Rev Immunol 9:729–740
Walport MJ (2001) Complement. First of two parts. N Engl J Med 344:1058–1066
Walport MJ (2001) Complement. Second of two parts. N Engl J Med 344:1140–1144
Huber-Lang M, Sarma JV, Zetoune FS et al (2006) Generation of C5a in the absence of C3: a new complement activation pathway. Nat Med 12:682–687
Riethmüller G, Meltzer M, Franklin E, Miescher PA (1966) Serum complement levels in patients with mixed (IgM-IgG) cryoglobulinaemia. Clin Exp Immunol 1:337–339
Linscott WD, Kane JP (1975) The complement system in cryoglobulinaemia. Interaction with immunoglobulins and lipoproteins. Clin Exp Immunol 21:510–519
Tanimoto K, Cooper NR, Johnsons JS, Vaughan JH (1975) Complement fixation by rheumatoid factor. J Clin Invest 55:437–445
Wilson MR, Arroyave CM, Miles L, Tan EM (1977) Immune reactants in cryoproteins. Relationship to complement activation. Ann Rheum Dis 36:540–548
Poskitt TR, Poskitt PK (1979) Temperature dependent activation of the alternate complement pathway by an IgG cryoglobulin. Am J Hematol 7:147–154
Tarantino A, Anelli A, Costantino A et al (1978) Serum complement pattern in essential mixed cryoglobulinaemia. Clin Exp Immunol 32:77–85
Greenstein JD, Peake PW, Charlesworth JA (1996) The metabolism of C9 in normal sbjects and in patients with autoimmune disease. Clin Exp Immunol 104:160–166
Ohsawa I, Ohi H, Tamano M et al (2001) Cryoprecipitate of patients with cryoglobulinemic glomerulonephritis contains molecules of the lectin complement pathway. Clin Immunol 101:59–66
D’Amico G, Colasanti G, Ferrario F, Sinico RA (1989) Renal involvement in essential mixed cryoglobulinemia. Kidney Int 35:1004–1014
Beddhu S, Bastacky S, Johnson JP (2002) The clinical and morphologic spectrum of renal cryoglobulinemia. Medicine (Baltimore) 81:398–409
Weiner SM, Prasauskas V, Lebrecht D et al (2001) Occurrence of C-reactive protein in cryoglobulins. Clin Exp Immunol 125:316–322
Schifferli JA, Taylor RP (1989) Physiological and pathological aspects of circulating immune complexes. Kidney Int 35:993–1003
Miller GW, Nussenzweig V (1975) A new complement function: solubilization of antigen-antibody aggregates. Proc Natl Acad Sci USA 72:418–422
Takahshi M, Tack BF, Nussenzweig V (1977) Requirements for the solubilization of immune aggregates by complement; assembly of a factor B-dependent C3-convertase on the immune complexes. J Exp Med 145:86–100
Schifferli JA, Amos N, Pusey CD et al (1983) Metabolism of autologous and homologous IgG in patients with mixed essential cryoglobulinemia type II. Absence of fast elimination of IgG. Clin Exp Immunol 51:305–316
Ng YC, Peters DK, Walport MJ (1988) Monoclonal rheumatoid factor-IgG immune complexes: poor fixation of opsonic C4 and C3 despite efficient complement activation. Arthritis Rheum 31:99–107
Schifferli JA, Ng YC, Estreicher J, Walport MJ (1988) The clearance of tetanus toxoid- anti tetanus toxoid immune complexes from the circulation of humans: Âcomplement- and erythrocyte CR1-dependent mechanisms. J Immunol 140:899–904
Madi N, Steiger G, Estreicher J, Schifferli JA (1991) Defective immune adherence and elimination of hepatitis B surface Ag/Ab complexes in patients with mixed essential cryoglobulinaemia type II. J Immunol 147:495–502
Schifferli JA, Steiger G, Polla L et al (1985) Activation of the alternative pathway of complement by skin immune deposits. J Invest Dermatol 85:407–411
Watanabe N, Akikusa B, Park SY et al (1999) Mast cells induce autoantibody-mediated vasculitis syndrome through tumor necrosis factor production upon triggering Fcgamma receptors. Blood 94:3855–3863
Guo S, Mühlfeld AS, Wietecha TA et al (2009) Deletion of activating Fcgamma receptors does not confer protection in murine cryoglobulinemia-associated membranoproliferative glomerulonephritis. Am J Pathol 175:107–118
Trendelenburg M, Fossati-Jimack L, Cortes-Hernandez J et al (2005) The role of complement in cryoglobulin-induced immune complex glomerulonephritis. J Immunol 175:6909–6914
Muhlfeld AS, Segerer S, Hudkins K et al (2004) Overexpression of complement inhibitor Crry does not prevent cryoglobulin-associated membranoproliferative glomerulonephritis. Kidney Int 65:1214–1223
Wietecha TA, Hudkins KL, Iyoda M et al (2006) Deletion of murine factor B in thymic stromal lymphopoietin mice aggravates cryoglobulin-associated membranoproliferative glomerulonephritis. J Am Soc Nephrol 17:F-PO820
Wietecha TA, Hudkins KL, Iyoda M et al (2007) Inhibition of complement pathways of the murine protein crry and deletion of factor B in thymic stromal lymphopoietin mice aggravates cryoglobulin-associated membranoproliferative glomerulonephritis. J Am Soc Nephrol 18:SA-PO317
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer-Verlag Italia
About this chapter
Cite this chapter
Trendelenburg, M. (2012). The Complement System in Cryoglobulinemia. In: Dammacco, F. (eds) HCV Infection and Cryoglobulinemia. Springer, Milano. https://doi.org/10.1007/978-88-470-1705-4_10
Download citation
DOI: https://doi.org/10.1007/978-88-470-1705-4_10
Published:
Publisher Name: Springer, Milano
Print ISBN: 978-88-470-1704-7
Online ISBN: 978-88-470-1705-4
eBook Packages: MedicineMedicine (R0)