PMID- 30192820 OWN - NLM STAT- MEDLINE DCOM- 20190225 LR - 20190225 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 13 IP - 9 DP - 2018 TI - The prevalence of antibodies against the HLA-DRB3 protein in kidney transplantation and the correlation with HLA expression. PG - e0203381 LID - 10.1371/journal.pone.0203381 [doi] LID - e0203381 AB - 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. FAU - Habets, Thomas H P M AU - Habets THPM AUID- ORCID: 0000-0003-0393-3394 AD - Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center +, Maastricht, The Netherlands. AD - Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center +, Maastricht, The Netherlands. FAU - Hepkema, Bouke G AU - Hepkema BG AD - Transplantation Immunology, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Kouprie, Niels AU - Kouprie N AD - Transplantation Immunology, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Schnijderberg, Melanie C A AU - Schnijderberg MCA AD - Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center +, Maastricht, The Netherlands. FAU - van Smaalen, Tim C AU - van Smaalen TC AD - Department of Surgery, Maastricht University Medical Center +, Maastricht, The Netherlands. FAU - Bungener, Laura B AU - Bungener LB AD - Transplantation Immunology, Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands. FAU - Christiaans, Maarten H L AU - Christiaans MHL AD - Department of Internal Medicine, Division of Nephrology, Maastricht University Medical Center +, Maastricht, The Netherlands. FAU - Bos, Gerard M J AU - Bos GMJ AD - Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center +, Maastricht, The Netherlands. AD - CiMaas BV, Maastricht, The Netherlands. FAU - Vanderlocht, Joris AU - Vanderlocht J AD - Department of Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center +, Maastricht, The Netherlands. AD - Department of Internal Medicine, Division of Hematology, Maastricht University Medical Center +, Maastricht, The Netherlands. AD - Central Diagnostic Laboratory, Maastricht University Medical Center +, Maastricht, The Netherlands. LA - eng PT - Journal Article DEP - 20180907 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antibodies) RN - 0 (Epitopes) RN - 0 (HLA Antigens) RN - 0 (HLA-DRB1 Chains) RN - 0 (HLA-DRB3 Chains) SB - IM MH - Alleles MH - Antibodies/*blood/immunology MH - Epitopes/genetics/metabolism MH - Gene Frequency MH - Graft Survival MH - HLA Antigens/*genetics/metabolism MH - HLA-DRB1 Chains/genetics/metabolism MH - HLA-DRB3 Chains/*genetics/immunology/metabolism MH - Histocompatibility Testing/methods MH - Humans MH - *Kidney Transplantation MH - Tissue Donors PMC - PMC6128541 COIS- 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. EDAT- 2018/09/08 06:00 MHDA- 2019/02/26 06:00 PMCR- 2018/09/07 CRDT- 2018/09/08 06:00 PHST- 2018/01/14 00:00 [received] PHST- 2018/08/20 00:00 [accepted] PHST- 2018/09/08 06:00 [entrez] PHST- 2018/09/08 06:00 [pubmed] PHST- 2019/02/26 06:00 [medline] PHST- 2018/09/07 00:00 [pmc-release] AID - PONE-D-17-45308 [pii] AID - 10.1371/journal.pone.0203381 [doi] PST - epublish SO - PLoS One. 2018 Sep 7;13(9):e0203381. doi: 10.1371/journal.pone.0203381. eCollection 2018.