RT Journal Article
SR Electronic
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
FD The Journal of Rheumatology
SP 1113
OP 1120
DO 10.3899/jrheum.091265
VO 37
IS 6
A1 ANNE FRIESGAARD CHRISTENSEN
A1 KIM HØRSLEV-PETERSEN
A1 STEPHAN CHRISTGAU
A1 HANNE MERETE LINDEGAARD
A1 TINE LOTTENBURGER
A1 KIRSTEN JUNKER
A1 MERETE LUND HETLAND
A1 KRISTIAN STENGAARD-PEDERSEN
A1 SØREN JACOBSEN
A1 TORKELL ELLINGSEN
A1 LIS SMEDEGAARD ANDERSEN
A1 IB HANSEN
A1 HENRIK SKJØDT
A1 JENS KRISTIAN PEDERSEN
A1 ULRIK BIRK LAURIDSEN
A1 ANDERS JØRGEN SVENDSEN
A1 ULRIK TARP
A1 JAN PØDENPHANT
A1 NIELS H.H. HEEGAARD
A1 AAGE VESTERGAARD
A1 ANNE GRETHE JURIK
A1 MIKKEL ØSTERGAARD
A1 PETER JUNKER
YR 2010
UL http://www.jrheum.org/content/37/6/1113.abstract
AB 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 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.