Uncoupling of collagen II metabolism in newly diagnosed, untreated rheumatoid arthritis is linked to inflammation and antibodies against cyclic citrullinated peptides

Anne Friesgaard Christensen, Kim Hørslev-Petersen, Stephan Christgau, Hanne Merete Lindegaard, Tine Lottenburger, Kirsten Junker, Merete Lund Hetland, Kristian Stengaard-Pedersen, Søren Jacobsen, Torkell Ellingsen, Lis Smedegaard Andersen, Ib Hansen, Henrik Skjødt, Jens Kristian Pedersen, Ulrik Birk Lauridsen, Anders Jørgen Svendsen, Ulrik Tarp, Jan Pødenphant, Niels H H Heegaard, Aage VestergaardAnne Grethe Jurik, Mikkel Ostergaard, Peter Junker

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

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 (rho = -0.25, p 0.002). CTX-II was increased (p < 0.001) and correlated positively with disease activity and radiographic progression, but not with anti-CCP (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.
Original languageEnglish
JournalThe Journal of Rheumatology
Volume37
Issue number6
Pages (from-to)1113-20
ISSN0315-162X
DOIs
Publication statusPublished - 1. Jun 2010

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