A spatial atlas of human gastro-intestinal acute GVHD reveals epithelial and immune dynamics underlying disease pathophysiology

Acute graft-versus-host disease (aGVHD) is a significant complication of allogeneic hematopoietic stem cell transplantation (aHSCT), driven by alloreactive donor T cells in the gut. However, the roles of additional donor and host cells in this process are not fully understood. We conducted multiplexed imaging on 59 biopsies from patients with gastrointestinal GVHD and 10 healthy controls, revealing key pathological changes, including fibrosis, crypt alterations, loss of Paneth cells, accumulation of endocrine cells, and disrupted immune organization, particularly a reduction in IgA-secreting plasma cells. Interestingly, CD8T cells were enriched only in a subset of patients, while others exhibited non-canonical enrichments of macrophages and neutrophils. Post-transplantation time significantly influenced immune composition, with host cells dominating plasma and T cell compartments long after transplantation. This spatial atlas of healthy duodenum and GVHD uncovers non-canonical immune dynamics, offering insights into disease pathophysiology and potential clinical applications in GVHD and other inflammatory bowel diseases.Competing Interest StatementD.M. received research grant from Novartis, CSL Behring and Sanofi, and consulting fee for Novartis, Incyte, Jazz Pharmaceutical, Therakos and Sanofi. G.S. is the recipient of an unrestricted research grant from Alexion.