Glomerular expression of matrix metalloproteinases in systemic lupus erythematosus in association with activity index and renal function

Abstract

Purpose: The aim of this study was to examine the expression of matrix metalloproteinases (MMPs) MMP-1, MMP-2, MMP-3, MMP-9, and their specific tissue inhibitor TIMP-1 in kidney biopsies of patients with lupus nephritis (LN) and to investigate the relationship between MMPs, activity index, and renal function at the time of kidney biopsy. Methods: We performed immunohistochemistry with monoclonal antibodies against MMP-1, MMP-2, MMP-3, MMP-9, and TIMP-1 in 58 kidney-biopsy specimens with LN (according to the 2004 ISN/RPS classification) and eight specimens from normal kidney tissue. We used clinical data of 36 patients at the time of kidney biopsy to evaluate the association between MMPs expression and renal function. Results: We found increased MMP-1, MMP-2, and MMP-3 expression in LN glomeruli and a significant correlation with the activity features, with higher activity index score and worse renal function (p < .001). In particular, we have noticed a significant correlation of MMP-1 with leukocyte influx (OR:16.5 95%CI 4.3–62.5 p < .001), and MMP-3 with glomerular hypercellularity (OR:18.6 95%CI 4.8–72.8 p < .001). Moreover, we found a strong correlation of MMP-2 expression with fibrinoid necrosis and cellular crescents formation (OR:17.1 95%CI 4.3–67.7 p < .001). Conclusions: MMP expression in renal biopsy of patients with LN is increased and directly related to a highly active inflammatory response. Moreover, stronger MMP expression is associated with higher activity index and a more profound renal dysfunction.

Keywords

• lupus nephritis
• matrix metalloproteinases
• mmp