Distinctive Transcriptional and Microbial Signature in Cutaneous Acute Graft-vs-Host-Disease

Abstract Skin acute graft-vs-host disease (aGVHD) is often first manifestation of GVHD, yet very few preclinical and clinical studies have focused on this target organ, leaving a critical information gap in the pathophysiology of GVHD. We hypothesized that analysis of host and microbiome gene expression could yield novel insights into the molecular and immunologic mechanisms underlying skin GVHD. Our objectives were to determine the differential host gene expression and microbiome profile of human skin aGVHD samples compared to normal skin, and aGVHD corticosteroid responders to non-responders. We performed RNA-Sequencing on lower arm biopsies from 45 patients compared to 10 healthy controls. Our findings suggest a distinctive transcriptional signature of cutaneous aGVHD, that could identify potentially actionable targets for prevention or treatment corticosteroid refractory disease. Our analysis suggests a key role of dendritic cells and macrophages, potentially mediated by differential expression of MIF, in the development of cutaneous aGVHD and corticosteroid responsiveness. Additionally, we describe a unique microbial signature in cutaneous aGVHD that includes skin microbes not previously described in this population. Competing Interest Statement The authors have declared no competing interest. Footnotes Data Availability: Datasets will be publicly available on Gene Expression Omnibus (GEO) with accession number GSE263557. Link to data specific repository page: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE263557 Code Availability statement: no additional custom code was generated for this analysis. Conflict of Interest: The authors declare no relevant conflict of interest. Funding: This research was supported by Marrow on the Move and Translational Team Science Award, University of Minnesota to NEJ. https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE263557