TY - JOUR T1 - Uncoupling of Collagen II Metabolism in Newly Diagnosed, Untreated Rheumatoid Arthritis Is Linked to Inflammation and Antibodies Against Cyclic Citrullinated Peptides JF - The Journal of Rheumatology JO - J Rheumatol DO - 10.3899/jrheum.091265 SP - jrheum.091265 AU - Anne Friesgaard Christensen AU - Kim Hørslev-Petersen AU - Stephan Christgau AU - Hanne Merete Lindegaard AU - Tine Lottenburger AU - Kirsten Junker AU - Merete Lund Hetland AU - Kristian Stengaard-Pedersen AU - Søren Jacobsen AU - Torkell Ellingsen AU - Lis Smedegaard Andersen AU - Ib Hansen AU - Henrik Skjødt AU - Jens Kristian Pedersen AU - Ulrik Birk Lauridsen AU - Anders Jørgen Svendsen AU - Ulrik Tarp AU - Jan Pødenphant AU - Niels H.H. Heegaard AU - Aage Vestergaard AU - Anne Grethe Jurik AU - Mikkel Østergaard AU - Peter Junker Y1 - 2010/05/01 UR - http://www.jrheum.org/content/early/2010/04/28/jrheum.091265.abstract N2 - Objective To investigate the relationship between markers of collagen II synthesis and degradation with disease activity measures, autoantibodies, and radiographic outcomes in a 4-year protocol on patients with early rheumatoid arthritis (RA) who are naïve to disease-modifying antirheumatic drugs. Methods One hundred sixty patients with newly diagnosed, untreated RA entered the Cyclosporine, Methotrexate, Steroid in RA (CIMESTRA) trial. Disease activity and radiograph status were measured at baseline and 4 years. The N-terminal propeptide of collagen IIA (PIIANP) and the cross-linked C-telopeptide of collagen II (CTX-II) were quantified at baseline by ELISA. PIIANP was also assayed at 2 and 4 years. Anticyclic citrullinated peptide (anti-CCP) was recorded at baseline. An uncoupling index for cartilage collagen metabolism was calculated from PIIANP and CTX-II measurements. Results PIIANP was low at diagnosis and 4 years on (p < 0.001), irrespective of treatment and disease activity. PIIANP was lowest in anti-CCP positive patients (p = 0.006), and there was a negative correlation between PIIANP and anti-CCP titers (ρ = –0.25, p 0.002). CTX-II was increased (p < 0.001) and correlated positively with disease activity and radiographic progression, but not with antiCCP (p = 0.93). The uncoupling index was not superior to CTX-II in predicting radiographic changes. Conclusion These results suggest that cartilage collagen formation and degradation are unbalanced when RA is diagnosed. The different associations of collagen II anabolism (PIIANP) and collagen II degradation (CTX-II) with anti-CCP, synovitis, and radiographic progression indicate that at this early stage of RA, cartilage collagen degradation is mainly driven by synovitis, while anti-CCP antibodies may interfere with cartilage regeneration by inhibiting collagen IIA formation. Trial registration j.nr NCT00209859. ER -