title: Deleterious impact of mismatching for human leukocyte antigen-C in presensitized recipients of kidney transplants.
abstract: BACKGROUND
  Allocation of deceased donor kidneys is commonly based on matching for human leukocyte antigen (HLA)-A, -B, and -DR, whereas HLA-C is currently disregarded. We investigated the influence of HLA-C compatibility on renal allograft survival. In addition, we tested an approach of matching for HLA-C epitopes.
  
  
  METHODS
  A cohort of 2260 deceased donor kidney transplants were typed for HLA-C using polymerase chain reaction-sequence specific primer method. Samples for DNA typing, serum results on presensitization (lymphocytotoxicity), and clinical data were provided by transplant centers participating in the Collaborative Transplant Study.
  
  
  RESULTS
  HLA-C mismatch was found to be associated with significantly decreased graft survival in presensitized (P<0.001) but not in non-presensitized (P=0.75) recipients. Mismatch of certain HLA-C epitopes seemed to be more influential than others, with mismatches showing a negative impact on graft survival in presensitized patients.
  
  
  CONCLUSIONS
  HLA-C mismatch has a substantial deleterious effect on graft survival in presensitized kidney recipients. Our study points out the need for investigations directed at identifying donor-specific HLA-C antibodies and evaluating their relevance in transplantation. In view of the fact that current assays for determining HLA-C specific antibodies are hampered by additional detection of clinically irrelevant antibodies, matching for HLA-C may provide a reasonable approach to improve transplant outcomes in presensitized kidney transplant recipients.
authors: Department of Transplantation Immunology, Institute of Immunology, University of Heidelberg, Heidelberg, Germany. hien.tran@med.uni-heidelberg.de
authors: Thuong Hien
authors: TH
authors: Tran
authors: Bernd
authors: B
authors: Döhler
authors: Andreas
authors: A
authors: Heinold
authors: Sabine
authors: S
authors: Scherer
authors: Andrea
authors: A
authors: Ruhenstroth
authors: Gerhard
authors: G
authors: Opelz
mesh_terms: D000328:Adult; D002102:Cadaver; D000939:Epitopes / Q000235:genetics; D005260:Female; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014019:Tissue Donors
chemical_list: D000939:Epitopes; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D007518:Isoantibodies