Chromatin accessibility of circulating CD8⁺ T cells differentiates disease severity in IgA nephropathy
Year: 2025
Type: article
Study design: Observational Study
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.
Source: Scientific Reports
Authors: Gwanghun Kim, Soojin Lee, Soojin Lee, Suk-Kyung Shin, Sehoon Park, Jung Hun Koh, Semin Cho, Yaerim Kim, Ik Soo Kim, Seung Jae Lee, Chaehwa Seo, Dong-Sup Lee, Hang-Rae Kim, Hyun Mu Shin, Dong Ki Kim, KORNERSTONE investigators, Yon Su Kim, Kwon Wook Joo, Kook-Hwan Oh, Hajeong Lee, Seung Seok Han, Yong Chul Kim, Eunjeong Kang, Hee Gyung Kang, Jung Pyo Lee, Jeonghwan Lee, Jung Tak Park, Ji In Park, Sunhwa Lee, Jin Kyung Kwon, Jin Ho Hwang, Nankyoung Lee, Eunyoung Kiim, Seung Hee Yang, Jeong Ho Joo, Jee-Yeon Ryu, Geon Woo Baek, Ara Ko, Jaeik Oh, Hyunah Ku
Institutions: Seoul National University, Eulji University Uijeongbu Eulji Medical Center, Janssen Korea (South Korea), Seoul National University Hospital, Chung-Ang University Gwangmyeong Hospital, Keimyung University, Gachon University, Samsung Medical Center, Research Institute for Future Medicine, Sungkyunkwan University, SNUH SMG-SNU Boramae Medical Center, Kangwon National University, Yonsei University, Kangwon National University Hospital, Yonsei University Health System, Chung-Ang University Hospital, Chung-Ang University, Korea Advanced Institute of Science and Technology
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,690
Awards: G1686845263, G7803178435
OpenAlex ID: W7117547521