Role of MMP-7 in the pathogenesis of systemic lupus erythematosus (SLE).

Systemic lupus erythematosus (SLE) is a clinically heterogeneous chronic, inflammatory autoimmune disorder. The association of MMP-7 and disease severity is still unclear. A total of 150 SLE patients and matched healthy controls were recruited for this study. Disease activity was scored according to SLEDAI (98 active and 52 inactive disease). Mean serum MMP-7 levels were significantly higher in SLE patients than controls ( p < 0.001). Patients with active disease showed higher levels (16.24 ± 6.2 ng/ml) as against inactive disease (10.50 ± 3.97 ng/ml) ( p ≤ 0.0001). Mean MMP-7 mRNA expression was significantly higher in patients (RQ = 3.16 ± 0.93) as compared to controls (RQ = 2.21 ± 0.89, p = 0.006). A positive correlation between MMP-7 levels, mRNA expression and SLEDAI score was observed ( r = 0.563, r = 0.427). The MMP-7 -181 G allele was found to be significantly higher among SLE patients ( p < 0.0001). A significant association was noted between MMP-7 -181 A/G +G/G genotypes with renal ( p = 0.0027) and CNS ( p = 0.0031) manifestations and anti-dsDNA autoantibodies ( p = 0.0312). Serum MMP-7 levels and mRNA expression were elevated in advanced stages of SLE, indicating that MMP-7 is associated with disease activity in SLE.

Expression of the matrix metalloproteinases MMP-2 and MMP-9 and their inhibitors TIMP-1 and TIMP-2 in systemic lupus erythematosus patients.

BACKGROUND: The study aimed to look at alterations in expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and their potential use as biomarkers in the pathogensis of SLE. METHODS: SLE patients (n = 41) and healthy controls (n = 50) were recruited. Quantitative RT-PCR/ELISA assays were performed for expression of MMP and TIMP mRNA in whole blood and PBMC; and corresponding serum protein levels. Intracellular levels of MMP-2 and MMP-9 proteins were analysed by flow cytometry. RESULTS: Based on SLEDAI scores patients were grouped into active (SLEDAI ≥ 10) and inactive cases (SLEDAI < 10). In active cases, MMP-2 expression significantly increased and TIMP-2 expression was decreased (p < 0.0001) both at serum secretion (p = 0.0003) and mRNA (p < 0.0001) levels as compared to inactive cases. MMP-9 and TIMP-1 showed significantly reduced serum secretion and mRNA expression (p < 0.0001) in active cases as compared to inactive cases. Intracellular concentration of MMP-9 was reported to be higher in neutrophils, while MMP-2 was mainly found in lymphocytes of SLE patients as compared to controls. MMP/TIMP ratio profile was altered as SLE disease progresses. INTERPRETATION & CONCLUSIONS: Findings suggest disturbed MMP and TIMP levels have a role in the pathogenesis of SLE.