title: Detection of antibodies against HLA-C epitopes in patients with rejected kidney transplants.
abstract: BACKGROUND
  Although HLA-C matching is not considered in kidney transplantation, several reports have shown that anti-HLA-C antibodies are associated with rejection and graft failure. DNA-based typing methods can now accurately determine HLA-C compatibility and sensitive assays such as Luminex with single alleles can identify HLA-C antibodies. HLA-C displays considerable amino acid polymorphism that can be translated into a structurally defined epitope repertoire.
  
  
  METHODS
  We have analyzed post-allograft nephrectomy sera from 45 HLA-C mismatched cases submitted by 15 laboratories worldwide participating in the 15th International Histocompatibility Workshop. All of them had HLA class I antibodies detected by a Luminex-based solid phase method using single-allele beads. This study addressed the determination of antibodies against donor HLA-C mismatches. Analysis of antibody reactivity patterns was performed using HLAMatchmaker, a structurally based matching program that considers 56 HLA-C eplets to define antibody-reactive epitopes. Many eplets shared by groups of HLA-C antigens, whereas others are also shared with HLA-A and/or HLA-B antigens.
  
  
  RESULTS
  Twenty-seven patients (60%) had donor-specific HLA-C antibodies, significantly less than the donor-specific antibodies induced by HLA-A and HLA-B mismatches. HLA-C antibody responses correlated with the eplet loads of the HLA-C mismatches. There were 352 instances whereby a donor HLA-C eplet was mismatched and for 84 (24%) of them there was antibody reactivity with a particular eplet (69 instances) or an eplet pair (15 instances). The latter generally consisted of mismatched eplets paired with self-eplets shared between the immunizing HLA-C alleles and HLA alleles of the patient. Several HLA-C eplets exhibited a relatively high immunogenicity as evidenced by their frequencies of specific antibodies.
  
  
  CONCLUSIONS
  These findings demonstrate the importance of HLA-C mismatching in humoral sensitization and that HLA-C epitopes can induce specific antibodies. They illustrate the usefulness of HLAMatchmaker in understanding donor-specific antibody reactivity patterns and the determination of HLA mismatch acceptability when transplantation is considered.
authors.affiliation: Division of Transplantation Pathology, Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA. duquesnoyr@upmc.edu
authors.forename: Rene J
authors.initials: RJ
authors.lastname: Duquesnoy
authors.forename: Marilyn
authors.initials: M
authors.lastname: Marrari
mesh_terms: D000465:Algorithms; D000917:Antibody Formation / Q000235:genetics / Q000276:immunology; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D015234:HLA-A Antigens / Q000737:chemistry / Q000276:immunology; D015235:HLA-B Antigens / Q000737:chemistry / Q000276:immunology; D015236:HLA-C Antigens / Q000737:chemistry / Q000276:immunology; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology; D008958:Models, Molecular
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D016056:Immunodominant Epitopes; D007518:Isoantibodies; C051138:anti-c antibody