Do recipient HLA alleles influence HLA Antibody Production in End- stage renal disease (ESRD)? A Scoping Review

Background Kidney transplantation is the primary choice of renal replacement therapy for patients with end-stage renal disease (ESRD). However, the development of anti-human leukocyte antigen (HLA) antibodies remains a significant immunological barrier to successful transplantation. While sensitization is often linked to previous exposure to alloantigens through pregnancy, transfusion, or prior transplants, the impact of the recipient’s HLA alleles on antibody formation has not been systematically reviewed. Methods A scoping review was conducted in accordance with PRISMA-ScR guidelines. A thorough search of major databases identified 469 studies. After removing duplicates and irrelevant records, 8 observational studies met the inclusion criteria and were included in the qualitative synthesis. The review examined the links between specific HLA alleles and the development of anti-HLA antibodies in ESRD patients. Results The HLA-DR alleles are believed to predict the strength of the alloimmune response, especially HLA-DRB1*01:01, -DRB1*14:01, -DRB1*15:01, -DR4, -DR5, -DR6, -DR52, and -DR53. Additional risk alleles include HLA-A3, -A36, -A66, -B18, and -B42. Conversely, DRB1*07:01, DRB1*11:01, -DRB1*13:01, and -B60 are identified as potentially protective against sensitization. Some studies also report that multi-locus haplotypes (e.g., DR1-B35-A2, DR7-B57-A1) have a stronger predictive value for sensitization risk than individual alleles. One study conducted in China found no significant differences in HLA allele distribution between sensitized and non-sensitized patients, suggesting potential population-based variation. Conclusions This review provides initial evidence that certain HLA alleles, especially at the HLA-DR locus, may influence the risk of anti-HLA antibody development in ESRD patients. Identifying both immunogenic and protective HLA alleles or haplotypes could enable more personalized immunological risk assessments for transplant candidates. Larger, prospective studies across diverse ethnic populations are required to validate these results and enhance transplant outcomes.