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

Autor: Habets THPM; Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center +, Maastricht, The Netherlands.; Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center +, Maastricht, The Netherlands., Hepkema BG; Transplantation Immunology, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Kouprie N; Transplantation Immunology, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Schnijderberg MCA; Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center +, Maastricht, The Netherlands., van Smaalen TC; Department of Surgery, Maastricht University Medical Center +, Maastricht, The Netherlands., Bungener LB; Transplantation Immunology, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Christiaans MHL; Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center +, Maastricht, The Netherlands., Bos GMJ; Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center +, Maastricht, The Netherlands.; CiMaas BV, Maastricht, The Netherlands., Vanderlocht J; Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center +, Maastricht, The Netherlands.; Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center +, Maastricht, The Netherlands.; Central Diagnostic Laboratory, Maastricht University Medical Center +, Maastricht, The Netherlands.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 Sep 07; Vol. 13 (9), pp. e0203381. Date of Electronic Publication: 2018 Sep 07 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0203381
Abstrakt: 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.
Competing Interests: Gerard M.J. Bos is CEO of CiMaas BV, Maastricht, a start-up/spin-off company of Maastricht University. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.
Databáze: MEDLINE
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