A study recently published in the journal Blood explored distinct spatial gene expression patterns in cellular compartments of lower gastrointestinal (GI) acute graft-versus-host disease (aGVHD) tissue and identified potential prognostic biomarkers, focusing on the USP17L gene family. The authors’ analysis served to understand the unique gene expression patterns in steroid-sensitive and steroid-resistant cases of lower GI aGVHD.
Samples were obtained from thirty-two treatment-blind patients with biopsy-confirmed lower GI aGVHD. To capture transcriptome profiles, researchers employed the GeoMxTM digital spatial profiler which analyzed data from over 18,000 genes across different tissue compartments including immune infiltrates, colonic epithelium, and vascular endothelium. Two clusters were further explored within each sampled tissue compartment and differential gene expression with spatial correlation of gene signatures was performed. In steroid-sensitive cases, the sampled tissue foci were dominated by classical cell-mediated immunity signatures, normal differentiated epithelial cells, and inflamed vasculature. Conversely, steroid-resistant cases exhibited an over-representation of a non-canonical inflammation characterized by a predominance of neutrophils, regenerative epithelial cells, and indications of angiogenic endothelial responses.
Furthermore, potential prognostic biomarkers were identified within the USP17L gene family as a predictor of poorer survival in patients with lower GI aGVHD, with the overexpression of USP17L family genes in immune cells being observed. These findings suggest that the USP17L family of genes may serve as a critical biomarker for assessing aGVHD patient outcomes. In summary, this study employed spatial transcriptomic technology to delineate unique cellular niches in lower GI aGVHD tissue, shedding light on distinct gene expression patterns. The study also showcased the potential of the USP17L gene family as a prognostic biomarker, which could aid in identifying patients at risk of poorer survival in the context of lower GI aGVHD.
Patel BK, Raabe MJ, Lang ER, et al. Spatial Transcriptomics Reveals Distinct Tissue Niches Linked with Steroid Responsiveness in Acute Gastrointestinal GVHD [published online ahead of print, 2023 Sep 12]. Blood. 2023;blood.2023020644.
Tags: GVHD, Graft versus host disease, grafts, graft, graft-versus-host disease