High serum levels of pro-matrix metalloproteinase-3 are associated with greater radiographic damage and the presence of the shared epitope in patients with rheumatoid arthritis

Abstract

Objective: To determine if there is a relationship between serum pro-matrix metalloproteinase-3 (proMMP-3) levels and radiographic damage in rheumatoid arthritis (RA), and to investigate whether high levels are associated with presence of the HLA-DRB1 shared epitope (SE).

Methods: Serum proMMP-3 levels were measured by ELISA on 45 RA patients with early disease and 292 with established disease. Early RA was arbitrarily defined as disease duration <3 years. Clinical and laboratory measures of disease activity and severity were obtained. Radiographic damage was assessed by scoring radiographs of the hands and feet using the method of Larsen. HLA-DRB1 typing was performed by sequence-specific oligonucleotide probing. Data were analyzed by multiple regression analysis.

Results: In all patients, there was a correlation (r = 0.318, p<0.0001) between serum proMMP-3 levels and Larsen scores. Other correlations were found with Health Assessment Questionnaire score (r = 0.261, p<0.0001) and C-reactive protein (CRP) (r = 0.357, p<0.0001) levels. ProMMP-3 levels were significantly higher in SE+/+ patients than in those completely lacking the SE, with the highest levels in patients carrying an HLA-DRI+/DR4+ phenotype. The greatest difference in proMMP-3 levels between SE+/+ and SE-/- patients was in those with a disease duration <3 years (381.6 vs. 71.7 ng/ml; p = 0.02).

Conclusion: Our data indicate that there is a significant relationship between radiographic damage and serum levels of proMMP-3. As well, higher circulating levels of proMMP-3 are found in patients positive for the SE, particularly in early RA, and this may partly explain the association between the SE and more erosive disease.