RESEARCH - IgG1 and IgG4 are the predominant subclasses among autoantibodies against two citrullinated antigens in RA

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Rheumatology Advance Access published online on August 13, 2008

Rheumatology, doi:10.1093/rheumatology/ken336

IgG1 and IgG4 are the predominant subclasses among auto-antibodies

against two citrullinated antigens in RA

R. Engelmann1, J. Brandt2,3, M. Eggert4, K. Karberg2, A. Krause5, G.

Neeck4 and B. Mueller-Hilke1

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.

Abstract

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.

http://rheumatology.oxfordjournals.org/cgi/content/abstract/ken336v1?papetoc

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