Diagnostic and prognostic signatures of glomerular membrane dysregulation in immune nephropathies

Background: Immunonephropathy, encompassing disorders such as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), and membranous nephropathy (MN), is characterized by immune-mediated glomerular injury leading to progressive renal dysfunction. Despite advances in clinical characterization, the precise molecular mechanisms underlying glomerular damage remain poorly understood. Methods: Gene expression profiles from the Gene Expression Omnibus (GEO) database were analyzed to identify plasma membrane homeostasis-related genes differentially expressed between immunonephropathy and healthy controls. Functional enrichment analyses were performed to investigate the biological pathways involved in disease progression. Least absolute shrinkage and selection operator (LASSO) regression and support vector machine (SVM) algorithms were used to identify diagnostic signature genes. Immune infiltration analysis and correlation analyses were further conducted to evaluate the associations between characteristic genes and clinical parameters, including estimated glomerular filtration rate (eGFR), proteinuria, and serum creatinine. Results: Differentially expressed plasma membrane homeostasis-related genes were identified in immunonephropathy. Functional enrichment analyses revealed significant enrichment of immune- and metabolism-related pathways. An eight-gene diagnostic signature consisting of IPMK, TP53, SLC40A1, NCOA4, SLC39A7, KEAP1, TNIP1, and SAT1 demonstrated high diagnostic accuracy. Immune infiltration analysis further revealed disease-specific immune profiles. Correlation analyses showed that KEAP1 and SLC40A1 were positively associated with proteinuria, whereas TNIP1 and TP53 were significantly associated with impaired renal function. Conclusions: Necroptosis, pyroptosis, and ferroptosis may be involved in glomerular injury in immunonephropathy. The identified characteristic genes provide insight into the molecular landscape of immunonephropathy and may serve as potential biomarkers for disease characterization.