The prevalence of antibodies against the HLA-DRB3 protein in kidney transplantation and the correlation with HLA expression

Thomas H. P. M. Habets, Bouke G. Hepkema, Niels Kouprie, Melanie C. A. Schnijderberg, Tim C. van Smaalen, Laura B. Bungener, Maarten H. L. Christiaans, Gerard M. J. Bos, Joris Vanderlocht*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)


Human leukocyte antigen (HLA)-DRB3 is a functional HLA class II gene, which has a limited allele diversity in the human population. Furthermore, the HLA-DRB3 gene is only present in a subset of individuals. Therefore, in organ transplantation, this HLA molecule is frequently mismatched between patient and graft donor and thus antibodies against this mismatched HLA molecule can develop. In this study, we aimed to evaluate the prevalence and reactivity of these antibodies and aimed to identify factors that underlie antibody formation against HLA-DRB3. We showed in our patient cohort that HLA-DRB3 antibodies are identified in about 7% of all patients that were screened with solid phase assays. In these assays, we observed multiple antibody reactivity patterns indicating that HLA-DRB3 harbours multiple epitopes. In those cases, where we succeeded at tracing back the induction of these antibodies to the molecular HLA typing of the immunogenic event, we noticed a different frequency of HLA-DRB1 allele groups in the donors as compared to a control group. To a certain extent this distribution (e.g. HLA-DRB1* 11 individuals) could be linked to an altered expression level. However, it also appears that different HLA-DRB3 alleles (e.g. HLA-DRB3* 01 group) vary in their immunogenicity without having an expression difference. In conclusion, our study provides information on the immunogenicity and reactivity patterns of antibodies against HLA-DRB3 in kidney transplantation, and it points towards the possibility of HLA expression as a factor underlying antibody formation.
Original languageEnglish
Article numbere0203381
Number of pages19
Issue number9
Publication statusPublished - 7 Sept 2018


  • LOCI
  • HLA-DRB3 Chains/genetics
  • Antibodies/blood
  • Gene Frequency
  • Humans
  • Graft Survival
  • Kidney Transplantation
  • HLA Antigens/genetics
  • Epitopes/genetics
  • HLA-DRB1 Chains/genetics
  • Alleles
  • Histocompatibility Testing/methods
  • Tissue Donors

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