Association between Serum Matrix Metalloproteinase- (MMP-) 3 Levels and Systemic Lupus Erythematosus: A Meta-analysis

Abstract

Introduction. Matrix metalloproteinase (MMP) is an emerging disease marker in rheumatic diseases. This is a meta-analysis aimed at systematically reviewing association between serum MMP-3 levels and systematic lupus erythematosus (SLE) activity, which sought to raise interest in MMP-3 as a putative biomarker. Methods. We conducted a meta-analysis of serum MMP-3 levels in patients with SLE and controls. We performed a PubMed search, EMBASE search, and forward search of the retrieved articles published until Oct. 1, 2018. In addition to this, we included data from a case-control study on a national pediatric SLE cohort, in which serum MMP-3 levels were measured in 11 SLE patients and 9 controls (unpublished). Subgroup analyses based on gender and disease activity were performed. Results. A total of 662 cases and 771 controls including 651 patients and 762 controls from 11 publications were studied. We observed significantly higher MMP-3 levels in SLE patients compared to healthy controls (P<0.001, Hedges’ g: 2.104, 95% CI 1.426-2.782). In subgroup analyses, we found a significant elevation of MMP-3 in the patients with nephritis compared to those without (P=0.006, Hedges’ g: 0.611, 95% CI 0.611-1.704). This finding was consistent between patients with persistent proteinuria and those without (P=0.023, Hedges’ g: 1.535, 95% CI 0.207-2.862). Meta-analysis showed no association between MMP-3 levels and gender or anti-double strand DNA antibody titer. Conclusions. Our meta-analysis demonstrated significantly higher MMP-3 levels in SLE patients than in controls and in patients with renal involvement than in those without.

A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics

“…HDQ interferes with the stimulatory effect of platelet aggregation even in the presence of a thrombin agonist [263]. MMPs are matrix metalloproteinases which are enzymes involved in extracellular matrix remodeling, and TIMPs are counter regulatory tissue inhibitors of MMPs [184,264] that have been extensively studied in SLE [185,265]. Research has shown that HDQ modulated MMPs-TIMPs interaction assisting in maintaining homeostasis of the extracellular matrix [266,267] and may thus play a role in reducing NETs.…”

Association of the Gelatinase B/Metalloproteinase 9 (MMP-9) Gene Haplotype in Systemic Lupus Erythematosus (SLE) in the Pediatric Egyptian Population

“…Despite the pathogenesis of SLE still not being entirely understood, investigations have pointed out its connection with deregulated MMPs [ 30 ]. In specific, Gelatinase B/MMP-9 involvement in SLE as a dangerous or advantageous molecule is still debatable because of contradictions in the published studies.…”

Integrative analysis of transcriptomic profiles reveals shared gene signatures of Rheumatoid Arthritis and Systemic Lupus Erythromatosus

“…MMP8 is believed to be one of the key regulators of tissue degradation and remodeling, which plays a central role in various important processes such as morphogenesis, tissue repair, wound healing and remodeling, in response to injury [41]. Various MMPs like MMP-2, MMP-3, and MMP-9 elevated level is reported for RA and SLE [27,42,43]. NFIL3 (E4BP4) is an important human transcription factor in autoimmune response, the over-expression of which leads to the downregulation of autoimmune responses in SLE patients via inhibiting the expression of CD40L [44] mutations in this gene can alter the immune hypothesis and sensitize for arthritis pathology [28].…”