title: Differences in immunogenicity of HLA antigens and the impact of cross-reactivity on the humoral response.
abstract: BACKGROUND
  Information about differences in immunogenicity of various HLA antigens may help guide donor selection and identify mismatches to avoid for patients likely to need retransplantation. To date, antibody responses to a wide array of individual mismatched antigens have not been evaluated.
  
  
  METHODS
  Frequencies of antibodies to mismatched HLA-A, HLA-B, HLA-DR, and HLA-DQ antigens were determined for 703 renal transplant patients who had no detectable donor-specific antibody before transplantation. The impact of cross-reactive group matching and production of antibodies cross-reactive with mismatched antigens were also assessed. Antibodies were identified using multiplexed bead assays.
  
  
  RESULTS
  The overall mean frequencies were similar for HLA-A (53.2%), HLA-DR (52.6%), and HLA-DQ (59.0%) antibodies, but significantly lower for HLA-B antibodies (42.4%). However, the response to individual antigens ranged from 15.0% to 76.2%. Antibody frequencies were reduced significantly for 54 of 62 specificities when the patient possessed an antigen cross-reactive with the donor mismatch, but the magnitude of the effect was variable and ranged from 8% to 83%. Moreover, there was directionality in the protective effect of cross-reactive group matching. Overall mean donor-specific antibody frequencies were comparable for men and women except for a significantly higher frequency of antibodies to HLA-DR among men (56.6% vs. 47.8%, P=0.004). Overall mean frequencies in blacks were higher than, or comparable to those of, whites, but differences were not significant.
  
  
  CONCLUSIONS
  There is considerable variability in the immunogenicity of different HLA antigens that is impacted by the presence or absence of cross-reactive antigens in the patient's phenotype. This information can be used to augment the immunologic evaluation of donor-recipient pairs.
authors.affiliation: 1 Immunogenetics Laboratory, Division of Immunogenetics and Transplantation Immunology, Department of Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Donna P
authors.initials: DP
authors.lastname: Lucas
authors.forename: Mary S
authors.initials: MS
authors.lastname: Leffell
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Zachary
mesh_terms: D001741:Black or African American; D015142:Baltimore; D003429:Cross Reactions; D000939:Epitopes; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006648:Histocompatibility; D006650:Histocompatibility Testing; D006801:Humans; D056724:Immunity, Humoral; D016130:Immunophenotyping; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D010641:Phenotype; D011237:Predictive Value of Tests; D016896:Treatment Outcome; D044465:White People
chemical_list: D000939:Epitopes; D006680:HLA Antigens; D007518:Isoantibodies