Sclerotic-type cutaneous chronic graft-versus-host disease (ScGvHD) is a severe complication of allogeneic hematopoietic stem cell transplantation, with profound morbidity. A dearth of effective, targeted treatment options necessitates further investigation into the molecular mechanisms underlying this T-cell-mediated disease. In this study, we compared the transcriptome in skin biopsies from pediatric and young adult (1.5 and false discovery rate/FDR<0.05. ScGvHD exhibited strong and significant Th1-skewing through key related cytokines and chemokines (CXCL9/10/11, IFN-γ, STAT1). Several markers related to the TSLP-OX40 axis were significantly upregulated relative to both controls and lesional AD, including OX40L, TSLP, and IL-33, as well as fibroinflammatory signatures characterized in a prior study in systemic sclerosis. Gene Set Variation Analysis reflected marker-level findings, showing greatest enrichment of the Th1 and fibroinflammatory pathways, with no global activation identified in Th2 or Th17/Th22. Cell-type deconvolution revealed significant representation of macrophages and vascular endothelial cells. ScGvHD in young patients may therefore be characterized by strong Th1-related upregulation with a unique TSLP-OX40 signature, suggesting new therapeutic avenues for this devastating disease.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
