Repeat donor HLA-DR mismatches in renal transplantation: is the increased failure rate caused by noncytotoxic HLA-DR alloantibodies?

Transplantation. 1999 Aug 27;68(4):589-91. doi: 10.1097/00007890-199908270-00027.

Abstract

Introduction: Data from the UCLA/UNOS and Collaborative Transplant Studies Registries indicate that mismatched HLA-DR alloantigens expressed on a former donor renal allograft should not be repeated because of significantly poorer long-term survival.

Methods: Retransplant candidates waiting for another renal allograft were screened for HLA class II alloantibodies (aAb) using direct complement-dependent cytotoxicity and several sensitive aAb binding assays.

Results: When screened by complement-dependent cytotoxicity, 46% of the patients were aAb negative. In contrast, using aAb binding assays, 90% of the patients had HLA-DR aAb specific for previous HLA-DR allograft mismatches. Most important, no directly cytotoxic HLA-DR antibody was detected in 9 of 27 patients.

Conclusion: Our studies suggest that crossing the same HLA-DR mismatch in a subsequent transplant may result in poorer survival due to underlying donor-specific HLA-DR aAb. If confirmed in a retrospective study of retransplant patients, B cell donor cross-matches using antiglobulin complement-dependent cytotoxicity or flow cytometry would appear essential if this barrier were to be crossed.

MeSH terms

  • Antibody Specificity
  • Complement System Proteins / immunology
  • Cytotoxicity Tests, Immunologic
  • Enzyme-Linked Immunosorbent Assay
  • Graft Rejection / etiology
  • Graft Rejection / immunology*
  • HLA-DR Antigens*
  • Histocompatibility Testing
  • Humans
  • In Vitro Techniques
  • Isoantibodies / blood*
  • Kidney Transplantation / adverse effects*
  • Kidney Transplantation / immunology*
  • Prognosis
  • Reoperation

Substances

  • HLA-DR Antigens
  • Isoantibodies
  • Complement System Proteins