ArticleScientific reports2025
Chromatin accessibility of circulating CD8⁺ T cells differentiates disease severity in IgA nephropathy.
Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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16 authors.
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Abstract
Immunoglobulin A (IgA) nephropathy (IgAN) is a prevalent primary glomerulonephritis with progressive potential. Early identification of high-risk patients is critical; however, current clinical and pathological markers are limited. This study aimed to identify epigenetic biomarkers in circulating CD8⁺ T cells that discriminate IgAN patients with different disease severity. Seventeen patients with biopsy-proven IgAN were stratified into early- and late-stage groups based on kidney function. CD8⁺ T cells were isolated and analyzed using transposase-accessible chromatin sequencing (ATAC-Seq) to assess chromatin accessibility. Differentially accessible regions (DARs) were identified and selected biomarkers were additionally analyzed with ATAC-qPCR. In total, 279 DARs were identified, of which 122 were selected as stage-specific biomarkers. CD8⁺ T cells from the early-stage group exhibited higher chromatin accessibility, and t-SNE showed a clear separation between the stages. Deconvolution analysis revealed the enrichment of naïve CD8⁺ T cells in the early-stage group and terminally differentiated effector memory CD8⁺ T cells in the late-stage group. Motif analysis uncovered distinct regulatory signatures: ETS1, LEF1, and RUNX2 in the early-stage, EOMES, TBX21, and IRF4 in the late stage. Receiver operating characteristic (ROC) analysis showed strong discriminatory power of the top biomarkers, enhanced by a composite weighted score. ATAC-qPCR confirmed the chromatin accessibility patterns observed using ATAC-Seq. This study defined stage-specific chromatin landscapes in the circulating CD8⁺ T cells of patients with IgAN and identified non-invasive epigenetic biomarkers associated with different disease severity, which may be utilized in early risk stratification and personalized management.
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