Tabu-Konzept 2.0: Homozygotie eines beliebigen HLA-Locus ist mit bestimmten HLA-Antikörpermustern assoziiert
Nils Lachmann (Berlin / DE), Claudia Lehmann (Leipzig / DE), Ramona Landgraf (Leipzig / DE), Henry Loeffer-Wirth (Leipzig / DE), Ilias Doxiadis (Leipzig / DE)
In a collaborative study of the University Hospital Leipzig and the Charité Berlin on a large cohort of kidney transplant recipients, we aimed to analyse the occurrence of HLA-specific antibody patterns with respect to the HLA repertoire of the patients.
Patients typed for the relevant HLA determinants using next generation sequencing. Antibody screening was performed by multiplex-based technology using microspheres coupled with the HLA alleles of HLA class I and II.
Patients homozygous for HLA-A*02, HLA-A*03, HLA-A*24, HLA-B*07, HLA-B*18, HLA-B*35, HLA-B*44, HLA-C*03, HLA-C*04, HLA-C*07 for class I and for class II: HLA-DRB1*01, HLA-DRB1*03, HLA-DRB1*07, HLA-DRB1*15, HLA-DQA1*01, HLA-DQA1*05, HLA-DQB1*02, HLA-DQB1*03(7), HLA-DQB1*06, HLA-DPA1*01, and HLA-DPB1*04 were found to have a significant higher antibody production compared to the heterozygous ones. All HLA determinants are affected. Remarkably, HLA-A*24 homozygous patients can produce antibodies towards all HLA-A determinants, while HLA-B*18 homozygous make antibodies towards all HLA-B and selected HLA-A and -C antigens and are associated with an elevation of HLA-DRB1, partly -DQB1, and -DPB1 alleles. Homozygosity for the HLA class II HLA-DRB1*01, and HLA-DRB1*15 seems to increase the risk for antibody responses against most of the HLA class I antigens (HLA-A, -B and -C) in contrast to HLA-DQB1*03(7) where a lower risk towards few HLA-A, and B alleles is observed.
The widely observed differential antibody response is to be accounted to the patient's HLA repertoire. Homozygous patients are at risk to produce HLA-specific antibodies hampering the outcome of transplantation or any substitution. Including this information in the allocation procedure might reduce antibody mediated immune reactivity and prevent graft loss. In addition, all patients in need of HLA based substitution and being homozygous in any of the HLA loci should treated in a way to avoid sensitization.
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