Differential association of the N-propeptide of collagen IIA (PIIANP) and collagen II C-telopeptide (CTX-II) with synovitis and erosions in early and longstanding rheumatoid arthritis.
OBJECTIVE
To determine the N-terminal propeptide of collagen IIA (PIIANP) in early and established rheumatoid arthritis (RA) and to study the association with collagen II degradation assessed by its C-telopeptide (CTX-II), x-ray status and disease activity measures.


METHODS
Two cohorts of RA patients were included: A) a one-year prospective cohort including 45 patients with early, untreated RA and B) a cross-sectional study comprising 50 RA patients with advanced disease. Blood donors and healthy volunteers served as controls. PIIANP in serum and urine CTX-II were measured by ELISA.


RESULTS
PIIANP did not differ from control levels at any time in patients with early RA (p=0.16 and p=0.89), but at one-year follow-up, PIIANP was decreased compared with baseline (p=0.046). In patients with longstanding RA, PIIANP was lower than in controls (p=0.002) and RA patients with a 12-month disease (p=0.01). PIIANP was unrelated to joint counts and CRP in both cohorts, but baseline PIIANP was lower among x-ray progressors than in non-progressors (p=0.04). CTX-II was persistently increased in both cohorts (p<0.001 and p<0.001). CTX-II was positively associated with joint counts and CRP but not with x-ray progression (p=0.84). There was no correlation between PIIANP and CTX-II.


CONCLUSIONS
Declining PIIANP with increasing RA duration and persistently increased CTX-II indicate that cartilage anabolic and degradative pathways are unbalanced from clinical RA onset. Furthermore, that collagen II depletion in RA is both mediated by anti-anabolic effects unassociated with synovitis (decreased PIIANP) and by excess collagen II degradation linked to synovitis (increased CTX-II).
Christensen
A F
AF
Departments of Rheumatology, Odense University Hospital, Odense and Institute of Clinical Research, University of Southern Denmark, Denmark. a.friesgaard@gmail.com
Lottenburger
T
T
Lindegaard
H
H
Christgau
S
S
Hørslev-Petersen
K
K
Junker
P
P
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000097:blood / Q000652:urine; D016022:Case-Control Studies; D024043:Collagen Type II / Q000097:blood* / Q000652:urine*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood* / Q000652:urine*; D011347:Procollagen / Q000097:blood*; D011446:Prospective Studies; D012720:Severity of Illness Index; D013585:Synovitis
D015415:Biomarkers; D024043:Collagen Type II; D010446:Peptide Fragments; D011347:Procollagen; C543437:collagen II C-telopeptide; C109195:procollagen type IIA amino-terminal peptide