Background In patients with rheumatoid arthritis (RA), seropositivity for either rheumatoid factor or anti-CCP antibodies has been identified as a predictive marker for treatment response to rituximab (RTX) in different studies. However, it is unclear, whether analysis of fine-reactivity against certain epitopes of citrullinated antigens or immunoglobulin subclass reactivity can contribute to the prediction of treatment response to RTX.
Objectives To investigate whether reactivity patterns against epitopes of the mutated citrullinated vimentin (MCV) antigen and/or anti-MCV subclass reactivities can contribute to differentiation of responders to RTX.
Methods Fine-reactivity against MCV was investigated in anti-MCV antibody positive patients with RA (n=34) under treatment with RTX. According to EULAR response criteria, 23 patients were classified as responders by reaching remission as defined by DAS28 <2.6 or low disease activity as defined by DAS28 <3.2. Follow-up analyses of anti-MCV response were performed using 88 synthetic overlapping MCV peptides in ELISA. The peptides used contained all known modifications of vimentin by mutation and citrullination1. In addition, influence of RTX treatment on anti-MCV IgG, IgM and IgA antibody reactivities was investigated by ELISA.
Results At baseline or during follow-up, none of the responders showed an anti-MCV IgA antibody response. In contrast, non-responders were positive for anti-MCV IgA in 50% of the cases at baseline and showed no reduction of antibody subclass reactivities in the follow-up. Furthermore, anti-MCV antibody subclass reactivities showed that RTX-responders were characterized by a reduction of anti-MCV IgG antibody titers, and by a normalization of anti-MCV IgM titers in all initially positive cases. At baseline, subsequent responders to RTX treatment were characterized by only a minor different epitope recognition pattern compared to non-responders. Remarkably upon treatment, a reduction of the number of recognized MCV epitopes was observed in 16 out of 23 responders (69.6%) in contrast to 3 out of 11 (27.3%) non-responders in follow-up analyses.
Conclusions Responders to RTX were characterized by a restricted immunoglobulin subclass reactivity against MCV lacking IgA anti-MCV antibodies at baseline, and a reduction of anti-MCV antibody titers as well as the epitope recognition pattern under treatment. Fine-reactivity against the MCV antigen can potentially contribute as a useful marker to predict response to RTX in anti-MCV positive RA patients.
Bang H, Egerer K, Gauliard A, Luthke K, Rudolph PE, Fredenhagen G, Berg W, Feist E, Burmester GR. Mutation and citrullination modifies vimentin to a novel autoantigen for rheumatoid arthritis. Arthritis Rheum. 2007 Jul 30;56(8):2503-2511
Disclosure of Interest L. Naumann Grant/Research support from: Roche Pharma AG, H. Bang Employee of: Orgentec, K. Egerer: None Declared, D. Meyer zum Büschenfelde: None Declared, B. Lehmann: None Declared, G. Fredenhagen Employee of: Orgentec, H. Bastian: None Declared, E. Wittenborn Employee of: Roche Pharma AG, G.-R. Burmester: None Declared, E. Feist: None Declared
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