A multiomics study used Mendelian randomization, single-cell RNA sequencing, and genetic data from European and Asian populations to identify proteins and immune-cell characteristics potentially involved in IgA nephropathy (IgAN). In European populations, complement factor H (CFH) was associated with lower IgAN risk, while CFHR1 and ERAP2 were associated with higher risk. Different signals emerged in Asian populations, including associations involving PYDC1, DEFA1/DEFA1B, PADI4, and RNASET2. Several immune-cell traits were also linked to disease susceptibility, reinforcing potential roles for complement, inflammation, and immune dysregulation in IgAN pathogenesis.
These findings point toward a future in which molecular biomarkers may help refine IgAN risk assessment and identify more targeted treatment approaches. Human plasma testing showed significantly higher levels of IDUA and PYDC1 in patients with IgAN than in healthy controls. Additional genetic and transcriptomic analyses supported several candidate pathways. However, the authors emphasize that these findings remain exploratory and hypothesis-generating: not all associations replicated across populations, several analyses had limited statistical power, and further functional and clinical validation is required before these markers can inform routine patient care.
Reference: You RL, Liu ZY, Li MS, et al. Comprehensive Analysis of IgA Nephropathy Causal Factors in Plasma Proteins, Immune Cell Types, and Immune Cell Traits. Clin J Am Soc Nephrol. 2026 Jun 1;21(6):1021-1035. doi: 10.2215/CJN.0000001022.
