Concentrations of circulating matrix metalloproteinase 9 inversely correlate with autoimmune antibodies to double stranded DNA: implications for monitoring disease activity in systemic lupus erythematosus

Abstract

Aims: To compare circulating matrix metalloproteinase (MMP) concentrations with antibodies to single and double stranded DNA (ssDNA and dsDNA) to determine their relation in inflammatory arthritic diseases, such as systemic lupus erythematosus (SLE).

Methods: Fibroblast MMP-2 and neutrophil MMP-9 were resolved by gelatin zymography and measured by densitometry. Anti-ssDNA and anti-dsDNA were determined by enzyme immunoassay and samples grouped on antibody content as follows: low anti-ssDNA/low anti-dsDNA antibodies (group 1); high anti-ssDNA/low anti-dsDNA antibodies (group 2); and high anti-ssDNA/high anti-dsDNA antibodies (group 3).

Results: Group 3 samples contained significantly lower amounts of MMP-9 when compared with group 1 samples. Higher molecular weight MMP-9 forms (130 and 225 kDa) were virtually absent. Group 2 samples contained intermediate MMP-9 concentrations. Fibroblast MMP-2 was unchanged in all groups. Mean complement C3 and C4 concentrations showed a consistent, but variably significant, decrease with increasing anti-ssDNA and anti-dsDNA antibodies. The mean erythrocyte sedimentation rate was raised in all patient groups.

Conclusions: Neutrophil MMP-9, an inflammatory marker, inversely correlates with anti-dsDNA antibodies, which are a specific marker for SLE, and may be important in monitoring disease activity during antibody deposition in tissues.

Figure 1

Gelatin zymography of matrix metalloproteinases (MMPs) in patient samples containing anti-DNA antibodies. (A) Low anti-ssDNA/low anti-dsDNA antibodies (group 1); (B) high anti-ssDNA/low anti-dsDNA antibodies (group 2); (C) high anti-ssDNA/high anti-dsDNA antibodies (group 3). Twelve samples/group were analysed. Sample number (1–12) are shown at the top. The position of the MMP molecular weight calibration markers is shown on the right.

Figure 2

Densitometric analysis of matrix metalloproteinases (MMPs). (A) 72 kDa MMP-2; (B) 225 kDa MMP-9; (C) 130 kDa MMP-9; and (D) 92 kDa MMP-9. Mean arbitrary densitometric units shown. Error bars indicate SD and the p values versus group 1 are shown (p<0.05, significant).