Roles of HLA-DRB107 :01 and HLA-B15 :01 in the risk of acute Graft Versus Host Disease in pediatric patients undergoing HSCT
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Graft Versus Host Disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplantation (HSCT). Previous studies suggest that genes coding for different components of the immune system, like human leukocyte antigen (HLA), may contribute to the development of GVHD. This study evaluates associations between patients’ HLA alleles and higher grades of acute (a) GVHD to identify potential marker of this HSCT complication. The HSCT pediatric patients recruited were distributed in discovery (n = 87) and replication (n = 154) cohorts. The genotypes were obtained through whole exome sequencing (WES) for discovery cohort and by allele specific PCR for associated alleles for replication cohort. Fifty-eight HLA alleles with carrier frequency above 5% were identified from WES data and analyzed with aGVHD grades II-IV. Two HLA alleles, HLA-DRB1*07:01 and HLA-B*15:01 , were associated with higher aGVHD risk, (p = 0.004 and p = 0.009, respectively). Stratifications according to the donor type revealed positive associations limited to HLA-matched unrelated donors (p = 0.007 and p = 0.0009, respectively). Furthermore, carriers of either HLA allele were more likely to have non-permissive HLA-DPB1 mismatches (p = 0.008 and p = 0.015, respectively). Overall, these findings could influence clinical decisions in donor selection, as the presence of HLA-B*15:01 and/or HLA-DRB1*07:01 might suggest the presence of a non-permissive HLA-DPB1 mismatch.