Researchers of a multimodal genetic study found that Crohn’s disease (CD) and IgA nephropathy (IgAN) share a meaningful immune-genetic relationship, with Mendelian randomization analyses in both European and East Asian populations showing that genetic liability to CD was associated with increased IgAN risk. Ulcerative colitis did not show the same consistent association. Genome-wide analyses also identified broad polygenic overlap between CD and IgAN, with shared signals concentrated in immune-related tissues and pathways rather than kidney-specific regulatory programs. ERAP2 and CARD9 emerged as leading candidate genes, supporting a proposed gut–immune–kidney framework involving antigen processing, mucosal immune dysregulation, and myeloid inflammatory signaling.
The clinical findings also supported the genetic signal: among 9,371 hospitalized patients with inflammatory bowel disease, biopsy-confirmed IgAN occurred more often in those with CD than in those with ulcerative colitis (0.53% vs 0.18%), with an age- and sex-adjusted odds ratio of 3.40. The findings support greater awareness of possible renal involvement in patients with CD, including attention to hematuria, proteinuria, and changes in kidney function. However, the authors caution that the data do not establish a direct one-way causal pathway. Shared genetic susceptibility may also explain part of the association, and prospective multicenter studies are needed before these findings can inform routine screening recommendations.
Reference: Su T, Liang M, Gao X, et al. Shared genetic architecture between Crohn’s disease and IgA nephropathy: implications for a gut-immune-kidney axis. Front Immunol. 2026 Aug 4;17:1905767. doi: 10.3389/fimmu.2026.1905767.
