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

Xingyu Liu, Yiyang Hu, Wenjia Zhang, Chaohong Nie, Fengxia Zhang, Yufeng Liu, Xiaoyan Su, Shuangxin Liu, Quhuan Li

Abstract read

In one paragraph

Article in Journal of translational autoimmunity, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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9 authors.

Xingyu LiuSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006, China.

Yiyang HuGuangdong Geriatric Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, China.

Wenjia ZhangSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006, China.

Chaohong NieThe First Clinical Medical School of Gannan Medical University, Ganzhou, Jiangxi Province, 341000, China.

Fengxia ZhangThe First Clinical Medical School of Gannan Medical University, Ganzhou, Jiangxi Province, 341000, China.

Yufeng LiuDepartment of Nephropathy, Dongguan Tungwah Hospital, Dongguan, Guangdong Province, 523015, China.

Xiaoyan SuDepartment of Nephropathy, Dongguan Tungwah Hospital, Dongguan, Guangdong Province, 523015, China.

Shuangxin LiuDepartment of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, China.

Quhuan LiSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

IgA nephropathyMendelian randomizationPlasma proteomicsProteome-wide association studySingle-cell transcriptome-wide association studyTranscriptome-wide association study

Identifiers

PMID42898749

DOI10.1016/j.jtauto.2026.100407

PMCPMC13678103

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