Lectin complement pathway components as risk factors for rheumatic heart disease in Assam, India

Abstract

Lectin complement pathway is an integral component of the innate immune response and has been associated with pathogenesis of rheumatic heart disease (RHD). Thus, we investigated the serum concentration and single nucleotide polymorphism (SNP) in different components of the lectin pathway to understand their role in susceptibility and progression of RHD. Sixty RHD patients and equal number of age and sex matched healthy controls from Assam Medical College and Hospital (AMCH), Assam were enrolled for the study. We analyzed mannose binding lectin (MBL2), Ficolin2, MBL-associated serine protease 2 (MASP2) and MBL-associated protein 44 (MAp44) for serum concentration using ELISA along with identification of gene polymorphism using nucleotide sequencing. MBL2 SNP rs11003125 was analyzed in the representative North-East India cohort and the GG genotype [OR=; 95% CI=, p < 0.05)] was observed to impart a protective effect against RHD. Promoter region variants of ficolin2 (−4 A > G) [p = 0.0181, OR 6.5102 (1.3764–30.7931)] were observed in RHD patients. Further, low serum levels of MASP2 (patients- 641.16 pg/ml, ±288.21; controls-1168.71 pg/ml, ±300.03) and high levels of MAp44 (patients- 70 pg/ml, ±31.5; controls-63.3 pg/ml ±17.9) were observed. Based on our results, −4 A > G variant in promoter region of FCN2 is associated with increased susceptibility and low serum levels of Ficolin2 in RHD patients. Elevated MAp44 levels and low MASP2 serum levels in patients suggest inhibition of activation of complement system and thus less clearance of pathogen in RHD. Overall, our study adds to the understanding on the role of lectin pathway proteins in the predisposition and progression of RHD.