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Open Access Research article

The fine specificity of IgM anti-citrullinated protein antibodies (ACPA) is different from that of IgG ACPA

Parawee Suwannalai1, Annemiek Willemze1, Linda van Toorn1, Gerrie Stoeken-Rijsbergen1, Nivine Levarht1, Jan Wouter Drijfhout2, Tom W J Huizinga1, Rene E M Toes1 and Leendert A Trouw1*

Author Affiliations

1 Department of Rheumatology, Leiden University Medical Center (LUMC), PO Box 9600, NL-2300 RC Leiden, The Netherlands

2 Department of Immunohematology and Blood Tranfusion, PO Box 9600, NL-2300 RC Leiden University Medical Center (LUMC), Leiden, The Netherlands

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Arthritis Research & Therapy 2011, 13:R195  doi:10.1186/ar3524

Published: 30 November 2011

Abstract

Introduction

The antigen recognition pattern of immunoglobulin M (IgM) could, when directed against protein antigens, provide an indication of the antigenic moieties triggering new B cells. The half-life of IgM is short and memory B cells against T-cell-dependent protein antigens typically produce IgG and not IgM antibodies. In this study, we analyzed whether a difference exists between the fine specificity of IgM versus IgG anti-citrullinated protein antibodies (ACPAs).

Methods

We determined the fine specificity of IgM and IgG ACPAs in 113 ACPA-positive rheumatoid arthritis patients with IgM cyclic citrullinated peptide 2 (CCP2) levels above 100 AU/ml. Fine specificity was assessed by performing ELISA using citrullinated peptides derived from vimentin, fibrinogen-β, fibrinogen-α and α-enolase, as well as citrullinated proteins fibrinogen and myelin basic protein. The arginine counterparts were used as controls.

Results

Recognition of defined citrullinated antigens by IgM ACPA was confined to samples that also displayed recognition by IgG ACPA. However, the IgM ACPA response displayed a more restricted antigen recognition profile than IgG ACPA (OR = 0.26, P < 0.0001).

Conclusion

Our data show that several defined citrullinated antigens are recognized only by IgG ACPA, whereas others are also recognized by IgM ACPA. These observations suggest that not all citrullinated antigens are able to activate new B cells despite concurrent recognition by IgG ACPA.