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

¹ Department of Laboratory Medicine, School of Medicine, University of Connecticut Health Center, Farmington, CT 06030, USA
² Farmington Valley Arthritis and Rheumatology, LLC, 54 West Avon Road, Avon, CT 06001, USA

Correspondence to:
Dr G S Makowski, Department of Laboratory Medicine, University of Connecticut Health Center, MC-2235, 263 Farmington Avenue, Farmington, CT 06030–2235, USA;
makowski{at}nso1.uchc.edu

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.

Keywords: anti-double stranded DNA antibodies; matrix metalloproteinases; systemic lupus erythematosus

Abbreviations: dsDNA, double stranded DNA; EIA, enzyme immunoassay; ESR, erythrocyte sedimentation rate; IFA, indirect immunofluorescent antibody test; MMP, matrix metalloproteinase; NGAL, neutrophil gelatinase associated lipocalin; SLE, systemic lupus erythematosus; SLEDAI, systemic lupus erythematosus disease activity index; ssDNA, single stranded DNA; TIMP, tissue inhibitor of metalloproteinases

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