Research Article For reprint orders, please contact: reprints@futuremedicine.com Role of MMP-2 and its inhibitor TIMP-2 as biomarkers for susceptibility to systemic lupus erythematosus Hemant J Vira 1 , Vandana D Pradhan 1 , Vinod D Umare 1 , Ajay K Chaudhary 1 , Anjali G Rajadhyksha 2 , Milind Y Nadkar 2 , Kanjaksha Ghosh 1 & Anita H Nadkarni* ,1 1 Department of Clinical & Experimental Immunology, National Institute of Immunohaematology, Indian Council of Medical Research, Mumbai 400012, India 2 Department of Medicine, King Edward Memorial Hospital, Mumbai 400012, India *Author for correspondence: Tel.: +22 241 385 1819; Fax: +22 2413 8521; anitahnadkarni@yahoo.com Aim: To investigate the possible association between MMP-2 (-1575 G/A, -1306 C/T) and its inhibitor TIMP-2 (-418 G/C) functional polymorphisms with development of severity in systemic lupus erythemato- sus (SLE) patients. Materials & methods: 150 SLE patients and matched healthy controls were recruited. Polymorphisms were detected by PCR-RFLP and serum levels by ELISA. Results: Mean MMP-2 and TIMP-2 serum level and mRNA expression were signifcantly increased in SLE cases as compared with controls (p < 0.0001). The concomitant presence of both MMP-2 1575A and its inhibitor TIMP-2 418C alleles syner- gistically increased the risk of SLE by 3.25-fold (CI: 1.44–7.34, p = 0.003). Conclusion: MMP-2, TIMP-2 and MMP-2/TIMP-2 ratios may act as biomarkers for susceptibility to SLE. First draft submitted: 28 March 2020; Accepted for publication: 15 May 2020; Published online: 24 September 2020 Keywords: autoantibodies • India • MMP-2 and TIMP-2 polymorphism • mRNA expression Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease characterized by lack of tolerance to self-tissues and production of autoantibodies against a wide range of self-antigens like histones, DNA, RNA, ribosomal proteins, and other nuclear components [1,2]. Matrix metalloproteinases (MMPs) participate primarily in the degradation and remodeling of the extracellular tissues, in cancers, joint destruction in arthritis [3]. The role of alteration in serum protein secretion and peripheral blood mononuclear cell (PBMC) mRNA levels of MMP-2 and its inhibitor TIMP-2 have been suggested in various autoimmune diseases like Wegener’s granulomatosis, multiple sclerosis, scleroderma and Sjogren’s syndrome [4–7]. Few studies have shown that the transcriptional activity of MMP-2 is affected by promoter polymorphisms in SLE [8]. Studies have been restricted to serum levels in Chinese and Israeli populations, which reported a higher level of MMP-2 [9–11] and also, studies carried out in Poland, Iran, Korea, Egypt as well as other studies carried out in China, which have reported a higher level of MMP-2 [12–16]. To our knowledge this is the first reported study of both the effects of MMP-2–G1575A promoter and its endogenous inhibitor TIMP-2–G418C polymorphisms simultaneously in the development of SLE and their association with clinical manifestations, autoantibody profile and inflammatory markers. Materials & methods A total of 150 SLE patients (135 females and 15 males) fulfilling the revised Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR criteria) (2012) was recruited along with 150 age and sex matched healthy controls (132 females and 18 males) without any concurrent infections [17]. The study was approved by the Institutional Ethics Committee (IEC) and written consent was taken from all patients and controls. Detailed information of each patient was noted in a pretested performa. Anti-nuclear antibodies (ANA) were detected by Indirect Immunofluorescence (IIF) method and serum complement components (C3; C4); hs-CRP levels were measured by Nephelometer (BN Prospec, Germany). Other laboratory parameters including estimation of serum creatinine, albumin, cholesterol, bilirubin, calcium levels and virological analyses (HBsAg, HIV, Biomark. Med. (2020) 14(12), 1109–1119 ISSN 1752-0363 1109 10.2217/bmm-2020-0180 C  2020 Future Medicine Ltd