Work

Integrating multiple omics approaches to identify AIF1 as a protective factor in IgA nephropathy

Year: 2026

Type: article

Abstract: IgA nephropathy (IgAN) is the most prevalent primary glomerular disease worldwide, and its diagnosis still relies on invasive kidney biopsy. To identify noninvasive biomarkers and therapeutic targets, we applied a multi-ancestry Mendelian randomization (MR) framework using proteome-wide association data from an Icelandic population, with validation in independent Fenland and United Kingdom cohorts, followed by transcriptomic, single-cell RNA sequencing (scRNA-seq), and cell-cell communication analyses. Nineteen candidate proteins were identified, and Bayesian colocalization supported a shared genomic region for eight, including AIF1. Transcriptomic analysis revealed downregulation of AIF1 in peripheral blood mononuclear cells from patients with IgAN, and scRNA-seq localized this depletion to dendritic cells (DCs), with partial restoration 150 days after tonsillectomy. Clinical phenotype MR showed inverse associations between AIF1 and hematuria and albuminuria, and enzyme-linked immunosorbent assay (ELISA) showed reduced circulating AIF1 in patients. AIF1 may protect against IgAN through DC-mediated antigen presentation, representing a candidate noninvasive biomarker and therapeutic target.

Source: Journal of Translational Autoimmunity

DOI: 10.1016/j.jtauto.2026.100407