Spatial Transcriptomic Signatures of Early Acute T Cell–mediated Rejection in Kidney Transplants

作者：Minji Kang, Haeyoon Kwon, Jeongin Song, Yunyoung Jang, Seung Hee Yang, Seung-Min Cha, Ji Hwan Moon, Yong Chul Kim, Hyun Je Kim · 发表于：Transplantation Direct · 年份：2024 · DOI：10.1097/txd.0000000000001705 · 被引用次数：5 · 研究领域：Renal Transplantation Outcomes and Treatments、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

Background. Kidney transplantation significantly improves the quality of life for those with end-stage renal failure, yet allograft rejection resulting from immune cell interactions remains a persistent challenge. Although T cell–directed immunosuppressive drugs effectively contain graft rejection in most patients, a notable proportion still experiences acute T cell–mediated rejection (TCMR). Despite an emphasis on suppressing T cell–mediated immune responses, successful control over TCMR is not always achieved, suggesting the potential involvement of factors beyond T cells. Methods. Biopsy samples from suspicious (borderline) for acute TCMR (borderline TCMR) and non-TCMR patients were obtained 9 d postsurgery, and spatial transcriptomics profiling was conducted using the GeoMx Digital Spatial Profiler platform. Regions of interest in the glomerulus and interstitium were selected on the basis of immunohistochemistry staining anti-CD3 to identify areas with T-lymphocyte infiltration. Differential gene expression analysis was performed using unpaired t tests. Results. Unbiased clustering of transcriptional profiles across all regions of interest showed distinct transcriptional profiles between glomeruli and interstitium in non-TCMR samples, whereas borderline TCMR samples displayed no distinct transcriptional profiles between these regions. Contrary to the prevailing T cell–centric view, we observed pathways and genes associated with innate immunity-related inflammatory conditi...