AUTHOR=Loeffler-Wirth Henry , Lehmann Claudia , Lachmann Nils , Doxiadis Ilias 

TITLE=Homozygosity in any HLA locus is a risk factor for specific antibody production: the taboo concept 2.0

JOURNAL=Frontiers in Immunology

VOLUME=15

YEAR=2024

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1384823

DOI=10.3389/fimmu.2024.1384823

ISSN=1664-3224

ABSTRACT=<sec><title>Objective</title><p>In a cooperative study of the University Hospital Leipzig, University of Leipzig, and the Charité Berlin on kidney transplant patients, we analysed the occurrence of HLA-specific antibodies with respect to the HLA setup of the patients. We aimed at the definition of specific HLA antigens towards which the patients produced these antibodies.</p></sec><sec><title>Methods</title><p>Patients were typed for the relevant HLA determinants using mainly the next-generation technology. Antibody screening was performed by the state-of-the-art multiplex-based technology using microspheres coupled with the respective HLA alleles of HLA class I and II determinants.</p></sec><sec><title>Results</title><p>Patients homozygous for <italic>HLA-A</italic>*<italic>02, HLA-A</italic>*<italic>03, HLA-A</italic>*<italic>24, HLA-B</italic>*<italic>07, HLA-B</italic>*<italic>18, HLA-B</italic>*<italic>35, HLA-B</italic>*<italic>44, HLA-C</italic>*<italic>03, HLA-C</italic>*<italic>04</italic>, and <italic>HLA-C</italic>*<italic>07</italic> in the class I group and <italic>HLA-DRB1</italic>*<italic>01, HLA-DRB1</italic>*<italic>03, HLA-DRB1</italic>*<italic>07, HLA-DRB1</italic>*<italic>15, HLA-DQA1</italic>*<italic>01, HLA-DQA1</italic>*<italic>05, HLA-DQB1</italic>*<italic>02, HLA-DQB1</italic>*<italic>03(7), HLA-DQB1</italic>*<italic>06, HLA-DPA1</italic>*<italic>01</italic>, and <italic>HLA-DPB1</italic>*<italic>04</italic> in the class II group were found to have a significant higher antibody production compared to the heterozygous ones. In general, all HLA determinants are affected. Remarkably, <italic>HLA-A</italic>*<italic>24</italic> homozygous patients can produce antibodies towards all HLA-A determinants, while <italic>HLA-B</italic>*<italic>18</italic> homozygous ones make antibodies towards all HLA-B and selected HLA-A and C antigens, and are associated with an elevation of <italic>HLA-DRB1, parts of DQB1 and DPB1 alleles. Homozygosity for the HLA class II HLA-DRB1*01</italic>, and <italic>HLA-DRB1</italic>*<italic>15</italic> seems to increase the risk for antibody responses against most of the HLA class I antigens (HLA-A, HLA-B, and HLA-C) in contrast to <italic>HLA-DQB1</italic>*<italic>03(7)</italic> where a lower risk towards few HLA-A and HLA-B alleles is found. The widely observed differential antibody response is therefore to be accounted to the patient’s HLA type.</p></sec><sec><title>Conclusion</title><p>Homozygous patients are at risk of producing HLA-specific antibodies hampering the outcome of transplantation. Including this information on the allocation procedure might reduce antibody-mediated immune reactivity and prevent graft loss in a patient at risk, increasing the life span of the transplanted organ.</p></sec>