A New Risk Score System for Early Warning Gastrointestinal Graft-Versus-Host Disease Based on the Immune Function of Mucosal-Associated Invariant T Cells

Abstract Gastrointestinal acute graft-versus-host disease (GI aGVHD) remains one of the major clinical challenges following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Early identification and intervention are critical to improving patient outcomes. Mucosal-associated invariant T (MAIT) cells are unconventional, mucosa-enriched T cells whose MR1-restricted, MHC-independent recognition may reduce GVHD risk. Our previous work showed that higher levels of donor-derived MAIT cells in grafts were associated with better immune reconstitution and a lower incidence of GI aGVHD. Single-cell RNA sequencing and murine transplant models revealed their functional heterogeneity in immune regulation, tissue repair, and chemotaxis—supporting their role as both biomarkers and therapeutic targets. In this prospective study, we used spectral flow cytometry to analyze MAIT cell phenotypes in peripheral blood stem cell grafts. Early MAIT cell reconstitution post-transplant strongly correlated with graft abundance, and lower MAIT cell levels were associated with increased GI aGVHD risk. Based on MAIT cell functional markers, we developed a three-marker predictive panel (CCR2, IL-4, IL-17A) that achieved an AUC of 0.80, increasing to 0.85 after adjusting for clinical covariates. This MAIT cell–based risk score enables pre-transplant risk stratification and early warning of GI aGVHD, offering strong clinical and translational value. Trial registration: ChiCTR2500095349.