title: The HLA-DR phenotype of the responder is predictive of humoral response against HLA class I antigens.
abstract: Recent studies suggest that the immunogenicity of an human leukocyte antigen (HLA) incompatibility should be considered in the context of the HLA phenotype of the recipient. The HLA-DR phenotype of the responder is thought to be predictive for the strength of the alloimmune response. In order to analyze the humoral response against HLA class I antigens in the context of the HLA-DR phenotype of the responder, we selected all HLA-DR homozygous Dutch patients that were present on the Eurotransplant waiting list between 1967 and 2000 (n=1,317 patients). By logistic regression it was determined whether antibody production against a specific HLA class I antigen is associated with a particular HLA-DR antigen in the patient. Furthermore, it was analyzed whether a patient, expressing a particular HLA-DR antigen, preferentially produces antibodies against particular HLA class I antigens. The results demonstrate that patients, homozygous for a certain HLA-DR antigen, cannot be considered high or low responders when analyzing the antibody response in terms of panel reactive antibody (PRA) value. However, a correlation can be found between the HLA-DR phenotype of the patient and the specific antibody response against HLA class I antigens. For example, antibodies against HLA-A10, -A11, -A19, and -B35 are produced more frequently by HLA-DR6 positive individuals, whereas antibodies against HLA-A3, -B5, -B7, -B8, and -B12 are produced more frequently by HLA-DR4 positive individuals. These data confirm that the HLA-DR phenotype of the responder plays a determinative role in the immunogenicity of mismatched HLA antigens. The results indicate that selection of HLA class I mismatches of the donor in the context of the HLA-DR phenotype of the responder might reduce the incidence of humoral graft rejection and minimize the sensitization grade of retransplant candidates.
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University, Leiden, The Netherlands. m.k.a.dankers@lumc.nl
authors.forename: Marlies K A
authors.initials: MK
authors.lastname: Dankers
authors.forename: Dave L
authors.initials: DL
authors.lastname: Roelen
authors.forename: Nico J D
authors.initials: NJ
authors.lastname: Nagelkerke
authors.forename: Peter
authors.initials: P
authors.lastname: de Lange
authors.forename: Guido G
authors.initials: GG
authors.lastname: Persijn
authors.forename: Ilias I N
authors.initials: II
authors.lastname: Doxiadis
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
mesh_terms: D000917:Antibody Formation; D015331:Cohort Studies; D005838:Genotype; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000032:analysis* / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000096:biosynthesis* / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D011237:Predictive Value of Tests
chemical_list: D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D007518:Isoantibodies