Novel immune cross-talk between inflammatory bowel disease and IgA nephropathy

Abstract

The mechanisms underlying the complex correlation between immunoglobulin A nephropathy (IgAN) and inflammatory bowel disease (IBD) remain unclear. This study aimed to identify the optimal cross-talk genes, potential pathways, and mutual immune-infiltrating microenvironments between IBD and IgAN to elucidate the linkage between patients with IBD and IgAN. The IgAN and IBD datasets were obtained from the Gene Expression Omnibus (GEO). Three algorithms, CIBERSORTx, ssGSEA, and xCell, were used to evaluate the similarities in the infiltrating microenvironment between the two diseases. Weighted gene co-expression network analysis (WGCNA) was implemented in the IBD dataset to identify the major immune infiltration modules, and the Boruta algorithm, RFE algorithm, and LASSO regression were applied to filter the cross-talk genes. Next, multiple machine learning models were applied to confirm the optimal cross-talk genes. Finally, the relevant findings were validated using histology and immunohistochemistry analysis of IBD mice. Immune infiltration analysis showed no significant differences between IBD and IgAN samples in most immune cells. The three algorithms identified 10 diagnostic genes, MAPK3, NFKB1, FDX1, EPHX2, SYNPO, KDF1, METTL7A, RIDA, HSDL2, and RIPK2; FDX1 and NFKB1 were enhanced in the kidney of IBD mice. Kyoto Encyclopedia of Genes and Genomes analysis showed 15 mutual pathways between the two diseases, with lipid metabolism playing a vital role in the cross-talk. Our findings offer insights into the shared immune mechanisms of IgAN and IBD. These common pathways, diagnostic cross-talk genes, and cell-mediated abnormal immunity may inform further experimental studies.

Keywords:

• Immunoglobulin a nephropathy
• inflammatory bowel disease
• cross-talk
• FDX1

Disclosure statement

The authors whose names are listed declare that the research was conducted in the absence of any commercial or financial relationship that could be construed as a potential conflict interest. The authors declare no competing interests.

Data availability statement

The code and data can be found on GitHub at the following link: https://github.com/qqyxasdq/Novel-Immune-Cross-talk-Between-IBD-and-IgAN.git

Additional information

Funding

This work was supported by the Young Scientists Fund of the National Natural Science Foundation of China [Grant No. 82103916], General Program of the National Science Foundation of China General Project [No. 81970633].