Multiple antibody reactivities to citrullinated antigens in sera from patients with rheumatoid arthritis: association with HLA-DRB1 alleles. Issue 5 (17th July 2008)

• Record Type: Journal Article
• Authors: Snir, O; Widhe, M; von Spee, C; Lindberg, J; Padyukov, L; Lundberg, K; Engström, Å; Venables, P J; Lundeberg, J; Holmdahl, R; Klareskog, L; Malmström, V
• Is Part Of: Annals of the rheumatic diseases. Volume 68:Issue 5(2009)
• Page Start: 736
• Page End: 743
• Publication Date: 2008-07-17
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2008.091355
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Autoantibodies to cyclic citrullinated peptides (anti-CCP) are present in most patients with rheumatoid arthritis (RA), and associate with HLA-DRB1 shared epitope (SE) alleles. Objective: To investigate reactivities of anti-CCP to various citrullinated proteins/peptides, which represent potential autoantigens in RA, and to examine the relationship between such antibodies, and their association with genetic variants within HLA-DRB1 SE alleles. Methods: Serum samples from 291 patients with established RA and 100 sex- and age-matched healthy subjects were included in this study. Sera were first analysed for presence of anti-CCP antibodies and further for IgG and IgA antibodies towards candidate autoantigens in both their native and citrullinated form including: fibrinogen, α-enolase peptide-1 and the C1-epitope of type II collagen (C1 III ). Antibody specificity was confirmed by cross-reactivity tests. HLA-DR genotyping was performed. Results: 72% of patients with RA were anti-CCP positive. Among the candidate autoantigens examined, IgG antibodies to citrullinated fibrinogen were found in 66% of patients' sera and in 41% for both citrullinated α-enolase peptide-1 and citrullinated C1 III . These antibodies were mainly seen in the anti-CCP-positive patient group; they were specific for their respective antigen and displayed limited cross reactivity. IgA responses were also detected, but less frequently than IgG. Anti-CCP and anti-citrullinated protein antibodies were associated with HLA-DRB1*04 rather than with HLA-DRB1*01 alleles. Conclusions: Antibodies directed against several citrullinated antigens are present in CCP-positive RA, with many patients displaying multireactivity. All specific reactivities were primarily associated with the HLA-DRB1*04 alleles, suggesting common pathways of anti-citrulline immunity.