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.
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).


CONCLUSIONS
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.
Cheung
N T
NT
Queen Mary's Hospital, Sidcup, Kent, UK.
Dawes
P T
PT
Poulton
K V
KV
Ollier
W E
WE
Taylor
D J
DJ
Mattey
D L
DL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000201:enzymology* / Q000276:immunology; D004792:Enzyme Precursors / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology*; D005260:Female; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008666:Metalloendopeptidases / Q000097:blood*; D008875:Middle Aged; D011859:Radiography
D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D004792:Enzyme Precursors; D000939:Epitopes; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D008666:Metalloendopeptidases; C048047:prostromelysin