Rheumatology Advance Access originally published online on August 13, 2008
Rheumatology 2008 47(10):1489-1492; doi:10.1093/rheumatology/ken336
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IgG1 and IgG4 are the predominant subclasses among auto-antibodies against two citrullinated antigens in RA
1Institute of Immunology, University of Rostock, Rostock, 2Practice for Rheumatology in Steglitz, 3Charité Medical University, Berlin, 4Center for Rheumatology at The Hospital Bad Doberan, Bad Doberan and 5Clinic for Rheumatology in Berlin-Wannsee, Berlin, Germany.
Correspondence to: R. Engelmann, Institute of Immunology, University of Rostock, Schillingallee 70, 18055 Rostock, Germany. E-mail: robby.engelmann{at}med.uni-rostock.de
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Abstract |
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Objective. Antibody subclasses reflect specific immunological processes and may be indicative of the underlying pathological pattern in an autoimmune disease like RA. We therefore quantified anti-cyclic citrullinated peptides (CCP) and anti- citrullinated vimentin (MCV) IgG subclass titres in RA patients and compared them with the respective titres of antibodies directed against the varicella zoster virus (VZV) and to total serum titres.
Methods. Sera of 77 patients fulfilling the ACR criteria for RA were collected. An IgG subclass-specific ELISA system was then established and combined with commercially available MCV, CCP and VZV pre-coated microtitre plates.
Results. Even though IgG1 is the predominant subclass among antibodies against CCP and MCV in RA patients, IgG4 is second with respect to titres and frequencies. This increase in IgG4 among RA-specific antibodies is independent of disease duration and does not reflect a general skewing of the immune response in these patients as overall serum titres and antibodies directed against VZV show a normal distribution of IgG1, IgG2, IgG3 and IgG4.
Conclusion. Elevated IgG4 titres are specific for auto-antibodies against citrullinated antigens in RA and are indicative of a Th2-biased environment during the generation of auto-reactive plasma cells. We discuss here an indirect role for IgG4 auto-antibodies in hindering the elimination of auto-reactive B and plasma cells and thus driving the autoimmune process.
KEY WORDS: Cyclic citrullinated peptides, Mutated citrullinated vimentin, Rheumatoid arthritis, Auto-antibodies, IgG subclasses
Submitted 29 April 2008;
revised version accepted 14 July 2008.
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