Integrated proteomic and metabolomic analysis identifies complement activation and metabolic alterations in the serum of patients with idiopathic membranous nephropathy: an exploratory study

Abstract

Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome in adults, yet its pathogenesis remains incompletely understood. This exploratory study aimed to characterize serum molecular profiles in IMN patients by integrating proteomics and metabolomics analyses, with the goal of generating hypotheses on pathophysiological mechanisms and potential candidate molecules. Serum samples from IMN patients and healthy controls were analyzed using label-free quantitative liquid chromatography–tandem mass spectrometry (LC–MS/MS) for proteomics (performed on pooled samples, three pools per group) and untargeted metabolomics (individual samples, n = 10 per group). Bioinformatics approaches were applied to identify differentially expressed proteins and metabolites, followed by pathway enrichment analysis. Targeted parallel reaction monitoring (PRM) was used to validate selected candidate proteins. A total of 103 differentially expressed proteins (64 up-regulated, 39 down-regulated) and 115 differential metabolites (33 up-regulated, 82 down-regulated) were identified. Proteomic analysis showed enrichment in the complement and coagulation cascades pathway. Metabolomic analysis indicated alterations in amino acid, lipid, and bile acid metabolism. Integrated analysis suggested possible convergent molecular disturbances at both the protein and metabolite levels. PRM validation preliminarily supported consistent up-regulation of F13B, APOB, CD14, ITIH3, EFEMP1, AMBP, PCOLCE, and LPA. This exploratory study reveals preliminary serum proteomic and metabolomic alterations in PLA2R-positive IMN, warranting validation in larger cohorts.