Levels of matrix metalloproteinase (MMP)-1 in paired sera and synovial fluids of juvenile idiopathic arthritis patients: relationship to inflammatory activity, MMP-3 and tissue inhibitor of metalloproteinases-1 in a longitudinal study.
OBJECTIVE
To measure levels of the collagenases matrix metalloproteinase (MMP)-1 and -13 in the synovial fluid (SF) and serum of patients with juvenile idiopathic arthritis (JIA), and to correlate these measurements with inflammatory activity, levels of the collagenase activator MMP-3 and the tissue inhibitor of metalloproteinases-1 (TIMP-1).


METHODS
Levels of MMP-1, -3, -13 and TIMP-1 were measured in paired SF and serum from 82 JIA patients using enzyme-linked immunsorbent assay and compared between subtypes and patients of different ages and disease durations. These levels were also correlated to the active joint count (AJC) and standard measures of inflammatory activity and therapeutic response, including erythrocyte sedimentation rate (ESR) and platelet count (PLT).


RESULTS
MMP-1 was detected in JIA SF and correlated with PLT. MMP-3 levels were high in SF and detectable in serum where they correlated with PLT, ESR and AJC. MMP-13, however, was not detected in SF or serum. No differences were observed between patients grouped by subtype, age or disease duration. MMP-3 contributed the majority of total MMP in SF samples resulting in excess MMP levels over TIMP-1.


CONCLUSIONS
MMP-1 is up-regulated in SF concordant with inflammatory activity in JIA. This was true for patients in all JIA subtypes and age groups, suggesting that the capability for degradation of type II collagen is present in early disease, and throughout the disease course. MMP-3 may be important in the activation of collagenases and the saturation of exogenous inhibitors. Serum MMP-3 may therefore be a useful, measurable and specific marker of active disease in JIA.
Peake
N J
NJ
Musculoskeletal Research Group, School of Clinical Medical Sciences, University of Newcastle-upon-Tyne, UK.
Khawaja
K
K
Myers
A
A
Jones
D
D
Cawston
T E
TE
Rowan
A D
AD
Foster
H E
HE
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D001171:Arthritis, Juvenile / Q000097:blood / Q000201:enzymology* / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D001799:Blood Sedimentation; D002097:C-Reactive Protein / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D020781:Matrix Metalloproteinase 1 / Q000097:blood / Q000378:metabolism*; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D010976:Platelet Count; D012720:Severity of Illness Index; D013582:Synovial Fluid / Q000201:enzymology*; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
D015415:Biomarkers; D019715:Tissue Inhibitor of Metalloproteinase-1; D002097:C-Reactive Protein; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1