Increased severity of acute graft versus host disease as a result of differential expression following a homozygous gene deletion

Summary Acute graft versus host disease ( aGvHD ) is a major cause of early morbidity post‐haematopoietic stem cell transplantation with minor histocompatibility antigens being a contributing factor. One mHA encoded by the UDP glycosyltransferase 2 family polypeptide B 17 ( UGT 2 B 17) gene has been shown to be immunogenic because of differential expression in the donor and recipient. We investigated the effects of a homozygous gene deletion of UGT 2 B 17 on the severity of acute aGvHD post‐ HSCT in HLA ‐matched related donors. 115 donor and recipient HLA and UGT 2 B 17 genotypes were determined using PCR‐SSO and PCR‐SSP , respectively. aGvHD grading was determined using routine criteria and dichotomized into either nonclinically significant (0–I) or clinically significant ( II–IV ). For all analyses, P ‐values of ≤ 0.05 were considered significant. The frequency of the gene deletion within the total cohort tested was 29.1%. A significant increase in aGvHD severity (grades II‐IV ) was seen in UGT 2 B 17 recipients expressing the protein when transplanted with a UGT 2 B 17 disparate donor ( P  = 0.011). We observed a significant association between UGT 2 B 17 expressing recipients and UGT 2 B 17 deficient donors with the severity of aGvHD . This study provides additional evidence that genomic variations may predispose to more severe aGvHD , but are not a mechanism for GvHD .