Rheumatoid Factor, Complement, and Mixed Cryoglobulinemia

Low serum level of complement component 4 (C4) that occurs in mixed cryoglobulinemia (MC) may be due to in vivo or ex vivo activation of complement by the classical pathway. Potential activators include monoclonal IgM rheumatoid factor (RF), IgG antibodies, and the complexing of the two in the cold,...

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Main Author: Peter D. Gorevic
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2012/439018
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author Peter D. Gorevic
author_facet Peter D. Gorevic
author_sort Peter D. Gorevic
collection DOAJ
description Low serum level of complement component 4 (C4) that occurs in mixed cryoglobulinemia (MC) may be due to in vivo or ex vivo activation of complement by the classical pathway. Potential activators include monoclonal IgM rheumatoid factor (RF), IgG antibodies, and the complexing of the two in the cold, perhaps modulated by the rheology and stoichiometry of cryocomplexes in specific microcirculations. There is also the potential for activation of complement by the alternative and lectin pathways, particularly in the setting of chronic infection and immune stimulation caused by hepatitis C virus (HCV). Engagement of C1q and interaction with specific cell surface receptors serve to localize immune complexes (ICs) to the sites of pathology, notably the cutaneous and glomerular microcirculations. Defective or saturated clearance of ICs by CR1and/or Fc receptors may explain persistence in the circulation. The phlogistic potential of cryoprecipitable ICs depends upon the cleavage of complement components to generate fragments with anaphylatoxin or leukocyte mobilizing activity, and the assembly of the membrane attack complex (C5b-9) on cell surfaces. A research agenda would include further characterization of the effector arm of complement activation in MC, and elucidation of activation mechanisms due to virus and viral antigens in HCV infection.
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spelling doaj-art-affcd49564a8427e8ed34830b0f468a12025-08-20T02:19:06ZengWileyClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/439018439018Rheumatoid Factor, Complement, and Mixed CryoglobulinemiaPeter D. Gorevic0Mount Sinai School of Medicine, Division of Rheumatalogy, Annenberg Building, Room 21-056, One Gustave L. Levy Place, New York, NY 10029-6574, USALow serum level of complement component 4 (C4) that occurs in mixed cryoglobulinemia (MC) may be due to in vivo or ex vivo activation of complement by the classical pathway. Potential activators include monoclonal IgM rheumatoid factor (RF), IgG antibodies, and the complexing of the two in the cold, perhaps modulated by the rheology and stoichiometry of cryocomplexes in specific microcirculations. There is also the potential for activation of complement by the alternative and lectin pathways, particularly in the setting of chronic infection and immune stimulation caused by hepatitis C virus (HCV). Engagement of C1q and interaction with specific cell surface receptors serve to localize immune complexes (ICs) to the sites of pathology, notably the cutaneous and glomerular microcirculations. Defective or saturated clearance of ICs by CR1and/or Fc receptors may explain persistence in the circulation. The phlogistic potential of cryoprecipitable ICs depends upon the cleavage of complement components to generate fragments with anaphylatoxin or leukocyte mobilizing activity, and the assembly of the membrane attack complex (C5b-9) on cell surfaces. A research agenda would include further characterization of the effector arm of complement activation in MC, and elucidation of activation mechanisms due to virus and viral antigens in HCV infection.http://dx.doi.org/10.1155/2012/439018
spellingShingle Peter D. Gorevic
Rheumatoid Factor, Complement, and Mixed Cryoglobulinemia
Clinical and Developmental Immunology
title Rheumatoid Factor, Complement, and Mixed Cryoglobulinemia
title_full Rheumatoid Factor, Complement, and Mixed Cryoglobulinemia
title_fullStr Rheumatoid Factor, Complement, and Mixed Cryoglobulinemia
title_full_unstemmed Rheumatoid Factor, Complement, and Mixed Cryoglobulinemia
title_short Rheumatoid Factor, Complement, and Mixed Cryoglobulinemia
title_sort rheumatoid factor complement and mixed cryoglobulinemia
url http://dx.doi.org/10.1155/2012/439018
work_keys_str_mv AT peterdgorevic rheumatoidfactorcomplementandmixedcryoglobulinemia