Background Rheumatoid arthritis (RA) is characterised by an overexpression of proinflammatory cytokines such as IL-1 and TNFa. These cytokines are known to stimulate the production of matrix degrading enzymes. The family of matrix metalloproteinases (MMP) are considered as key enzymes in the destruction of cartilage and bone. One of the most abundant MMP found in RA is MMP-3. It is well established that levels of MMP-3 in peripheral blood are highly correlated with disease activity in RA. Furthermore high plasma levels of MMP-3 account for an early erosive form of RA. It was the aim of our study to determine whether there exist an association between plasma MMP-3 levels and the presence of the shared epitope (SE) and an association of MMP-3 levels in plasma samples and bone extracts.
45 RA patients were included in this study. HLA-DRB genotyping with DNA from peripheral blood was performed using sequence-specific primers and reverse hybridisation provided by AID GmbH Strassberg. Plasma MMP-3 concentrations were determined applying the biotrak MMP-3 ELISA system by Amersham Pharmacia Biotech.
Our results show significant differences in plasma MMP-3 levels in RA patients depending on the presence of the shared epitope. The mean MMP-3 levels were significantly elevated in the SE positive compared to the SE negative group (99.50+13.74 ng/ml vs. 43.02+9.23 ng/ml, mean+SEM, p = 0.012 Mann Whitney U-test). The highest MMP-3 levels were found in patients with those allels encoding the amino acid sequence QRRAA at the position 70–74 in the third hypervariable region of the HLA-DRB1 molecule, i.e. *0101, *0102, *0404 and *0405. The MMP-3 levels in this group (139.99+27.25 ng/ml) were significantly higher compared not only to the SE negative group (p = 0.011) but also compared to the group with the SE QKRAA (68.17+6.53 ng/ml, p = 0.032).
Concentrations of MMP-3 in the extract of non-collagenous proteins from defatted bone powder were shown to be strongly correlated to levels in corresponding plasma samples (r = 0.57, p < 0.001), suggesting that plasma MMP-3 levels reflect at least in part the local situation in bone.
Our data indicate that plasma MMP-3 levels in RA may reflect the situation in the bone and vary according to the presence of the shared epitope. This results may explain the association of early erosive RA with the presence of SE.
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