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. 2007 Nov;66(11):1450-5.
doi: 10.1136/ard.2006.062919. Epub 2007 May 1.

Autoantibodies binding to citrullinated telopeptide of type II collagen and to cyclic citrullinated peptides predict synergistically the development of seropositive rheumatoid arthritis

Marja-Kaisa Koivula  1 , Markku Heliövaara, Jarmo Ramberg, Paul Knekt, Harri Rissanen, Timo Palosuo, Juha Risteli
Affiliations

Autoantibodies binding to citrullinated telopeptide of type II collagen and to cyclic citrullinated peptides predict synergistically the development of seropositive rheumatoid arthritis

Marja-Kaisa Koivula et al. Ann Rheum Dis. 2007 Nov.

Abstract

Objectives: To find out whether autoantibodies to citrullinated telopeptides of type I and II collagens and to cyclic citrullinated peptides (CCPs) predict the development of rheumatoid arthritis (RA).

Methods: A case-control study (matched for sex, age and municipality) was nested within a Finnish cohort of 19072 adults who had neither arthritis nor a history of it at the baseline examination during 1973-7. 124 subjects developed RA by late 1989, and of these, 89 were positive for rheumatoid factor (RF). Preillness serum specimens were analysed for autoantibodies against arginine (A)- or citrulline (C)-containing synthetic telopeptides using a chemiluminescence method and for anti-CCPs Mark2 with an enzyme-linked immunosorbent assay method.

Results: The mean levels of autoantibodies to citrulline-containing telopeptides and the C/A ratios of type I and II collagens and to CCP were higher in subjects who later developed RF-positive RA. In the highest tertiles of C/A (I), C/A (II) ratios and anti-CCPs levels, the relative risk of RF-positive RA was significantly increased. In the multifactorial model, only anti-CCPs retained its statistical significance. However, the interaction term of C/A (II) ratio and anti-CCPs proved to be statistically significant (p = 0.02). The subjects ranked into the highest tertiles of both C/A (II) ratio and anti-CCPs had an odds ratio of 20.06 (95% confidence interval, 4.37 to 92.06) of developing RF-positive RA compared with those in the lowest tertiles of these antibodies. None of the autoantibodies predicted RF-negative RA.

Conclusion: Autoantibodies to citrullinated telopeptides of type I and II collagen and to CCPs exert a synergistic effect on the risk of seropositive RA.

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Conflict of interest statement

Competing interests: None declared.

References

    1. Aho K, Heliövaara M. Risk factors for rheumatoid arthritis. Ann Med 200436242–251. - PubMed
    1. Manfredsdottir V F, Vikingsdottir T, Jonsson T, Geirsson A J, Kjartansson O, Heimisdottir M.et al The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis. Rheumatology (Oxford) 200645734–740. - PubMed
    1. Klareskog L, Stolt P, Lundberg K, Kallberg H, Bengtsson C, Grunewald J.et al A new model for an etiology of rheumatoid arthritis: smoking may trigger HLA‐DR (shared epitope)‐restricted immune reactions to autoantigens modified by citrullination. Arthritis Rheum 20065438–46. - PubMed
    1. Nijenhuis S, Zendman A J W, Vossenaar E R, Pruijn G J M, van Venrooij W J. Autoantibodies to citrullinated proteins in rheumatoid arthritis: clinical performance and biochemical aspects of an RA‐specific marker. Clin Chem Acta 200435017–34. - PubMed
    1. Yamada R, Suzuki A, Chang X, Yamamoto K. Citrullinated proteins in rheumatoid arthritis. Front Biosci 20051054–64. - PubMed

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