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Peer-reviewedCC BYJournal of translational autoimmunity

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

  • Xingyu Liu1,2
  • Yiyang Hu3,4
  • Wenjia Zhang1
  • Chaohong Nie5
  • Fengxia Zhang5
  • Yufeng Liu6
  • Xiaoyan Su6
  • Shuangxin Liu7
  • Quhuan Li1
7 affiliations
  1. 1School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, 510006, China.
  2. 2Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, China.
  3. 3Guangdong Geriatric Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, China.
  4. 4Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, China.
  5. 5The First Clinical Medical School of Gannan Medical University, Ganzhou, Jiangxi Province, 341000, China.
  6. 6Department of Nephropathy, Dongguan Tungwah Hospital, Dongguan, Guangdong Province, 523015, China.
  7. 7Department of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou, 510080, China.
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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.

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Cite

BibTeXRIS
BibTeX
@article{liu2026integrating,
  title = {{Integrating multiple omics approaches to identify AIF1 as a protective factor in IgA nephropathy.}},
  author = {Xingyu Liu and Yiyang Hu and Wenjia Zhang and Chaohong Nie and Fengxia Zhang and Yufeng Liu and Xiaoyan Su and Shuangxin Liu and Quhuan Li},
  journal = {Journal of translational autoimmunity},
  year = {2026},
  month = oct,
  doi = {10.1016/j.jtauto.2026.100407},
  url = {https://europepmc.org/article/MED/42898749},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Integrating multiple omics approaches to identify AIF1 as a protective factor in IgA nephropathy.
AU  - Xingyu Liu
AU  - Yiyang Hu
AU  - Wenjia Zhang
AU  - Chaohong Nie
AU  - Fengxia Zhang
AU  - Yufeng Liu
AU  - Xiaoyan Su
AU  - Shuangxin Liu
AU  - Quhuan Li
PY  - 2026
DA  - 2026/10/07
JO  - Journal of translational autoimmunity
DO  - 10.1016/j.jtauto.2026.100407
UR  - https://europepmc.org/article/MED/42898749
AB  - 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.
SN  - 2589-9090
ER  -