Immune and Metabolic Pathways in Idiopathic Membranous Nephropathy: Insights from Bioinformatics and Animal Models

Abstract Idiopathic membranous nephropathy (IMN) is an autoimmune disease primarily driven by immune mechanisms. Recent studies have highlighted the involvement of metabolic pathways, particularly lipid metabolism and immune response, in IMN pathogenesis. This study aimed to investigate the interplay between immunity and metabolism in IMN through bioinformatic analyses of immune infiltration patterns and differentially expressed genes (DEGs), with validation using a passive Heymann nephritis (PHN) rat model. Our findings revealed a disrupted immune microenvironment in IMN patients compared to healthy controls. Single-cell analysis of kidney tissue from IMN patients identified significant activation of the steroid biosynthesis pathway in monocytes. Among the DEGs linked to both immunity and metabolism, INPP5D was notably upregulated in IMN, with monocytes exhibiting the highest expression levels. Additionally, PHN rats demonstrated increased iNOS expression, indicative of M1 macrophage recruitment, alongside elevated SHIP1 expression. These results underscore the potential role of SHIP1 in modulating immune responses and influencing IMN prognosis. Focusing on SHIP1’s involvement in IMN pathogenesis and its impact on immune regulation may enhance the understanding of IMN risk factors and support the development of targeted therapeutic strategies.