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

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Τίτλος: The prevalence of antibodies against the HLA-DRB3 protein in kidney transplantation and the correlation with HLA expression
Συγγραφείς: Habets, Thomas H. P. M., Hepkema, Bouke G., Kouprie, Niels, Schnijderberg, Melanie C. A., van Smaalen, Tim C., Bungener, Laura B., Christiaans, Maarten H. L., Bos, Gerard M. J., Vanderlocht, Joris
Πηγή: Habets, T H P M, Hepkema, B G, Kouprie, N, Schnijderberg, M C A, van Smaalen, T C, Bungener, L B, Christiaans, M H L, Bos, G M J & Vanderlocht, J 2018, 'The prevalence of antibodies against the HLA-DRB3 protein in kidney transplantation and the correlation with HLA expression', PLOS ONE, vol. 13, no. 9, e0203381. https://doi.org/10.1371/journal.pone.0203381
Έτος έκδοσης: 2018
Συλλογή: Maastricht University Research Publications
Θεματικοί όροι: ALLELES, GENES, LOCI, MOLECULES, FAILURE, SPECIFICITY, SEQUENCES, ANTIGENS, HISTORY, DISEASE, HLA-DRB3 Chains/genetics, Antibodies/blood, Gene Frequency, Humans, Graft Survival, Kidney Transplantation, HLA Antigens/genetics, Epitopes/genetics, HLA-DRB1 Chains/genetics, Histocompatibility Testing/methods, Tissue Donors
Περιγραφή: 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.
Τύπος εγγράφου: article in journal/newspaper
Γλώσσα: English
ISSN: 1932-6203
Relation: info:eu-repo/semantics/altIdentifier/pmid/30192820; info:eu-repo/semantics/altIdentifier/wos/000444093600066; info:eu-repo/semantics/altIdentifier/pissn/1932-6203
DOI: 10.1371/journal.pone.0203381
Διαθεσιμότητα: https://cris.maastrichtuniversity.nl/en/publications/9702eeb3-d41e-4eaf-a03b-3adca4cb1055
https://doi.org/10.1371/journal.pone.0203381
Rights: info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/
Αριθμός Καταχώρησης: edsbas.206BA8D1
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  Data: The prevalence of antibodies against the HLA-DRB3 protein in kidney transplantation and the correlation with HLA expression
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  Data: Habets, T H P M, Hepkema, B G, Kouprie, N, Schnijderberg, M C A, van Smaalen, T C, Bungener, L B, Christiaans, M H L, Bos, G M J & Vanderlocht, J 2018, 'The prevalence of antibodies against the HLA-DRB3 protein in kidney transplantation and the correlation with HLA expression', PLOS ONE, vol. 13, no. 9, e0203381. https://doi.org/10.1371/journal.pone.0203381
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  Data: 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.
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