The HLA-DR phenotype of the responder is predictive of humoral response against HLA class i antigens

Marlies K.A. Dankers, Dave L. Roelen, Nico J.D. Nagelkerke, Peter De Lange, Guido G. Persijn, Ilias I.N. Doxiadis, Frans H.J. Claas

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)13-19
Number of pages7
JournalHuman Immunology
Volume65
Issue number1
DOIs
Publication statusPublished - Jan 2004

Keywords

  • Antibodies
  • HLA-DR
  • Immunogenicity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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