Introduction: Associations of variations in PLA2R1 and HLA-DQA1 genes with susceptibility to idiopathic membranous nephropathy (IMN) have been well documented. Association with spontaneous remission, however, is poorly defined in the Chinese Han population. Methods: A Chinese cohort of 117 IMN patients and 138 healthy controls were recruited between July 2009 and November 2019. Case-control studies for single-nucleotide polymorphisms (SNPs) within HLA-DQA1 (rs2187668) and PLA2R1 (rs35771982, rs4664308, rs3749117, rs3749119) genes were performed. The contributions of these polymorphisms to predict susceptibility, titre of autoantibodies against the M-type phospholipase A2 receptor (anti-PLA2R1), glomerular PLA2R1 expression, and spontaneous remission were analysed. Results: We found that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) were strongly associated with IMN susceptibility, while SNP (rs2187668) within HLA-DQA1 did not increase the risk of IMN. All SNPs in PLA2R1 and HLA-DQA1 were not statistically associated with anti-PLA2R1 titre, glomerular PLA2R1 expression and spontaneous remission after Bonferroni correction (P>0.0167). Clinical and pathological parameters such as lower levels of serum albumin, higher levels of anti-PLA2R1 and glomerular PLA2R1 expression were independent risk factors for non-spontaneous remission. Conclusion: This study confirms that variations in PLA2R1 (SNPs rs35771982, rs4664308, rs3749117) are risk factors for IMN. We found excellent association of serum albumin level, anti-PLA2R1 titre and glomerular PLA2R1 positivity with non-spontaneous remission in IMN.
Membranous nephropathy is an organ-specific autoimmune disease and is the most common cause of adult-onset nephrotic syndrome. The diagnosis of membranous nephropathy mainly depends on pathological characteristics observed through various techniques such as diffuse thickening of the glomerular basement membrane and spike formation by light microscopy, granular deposition of immunoglobulin G (IgG) and complement 3, along with the glomerular capillary loops by immunofluorescence, and subepithelial electron-dense deposits by electron microscopy. In recent years, the discovery of M-type phospholipase A2 receptor (PLA2R1) and demonstration of its function in idiopathic membranous nephropathy (IMN) have played an important role in distinguishing IMN from secondary membranous nephropathy and predicting the treatment efficacy and kidney outcome in IMN patients as well.
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