title: Repeat donor HLA-DR mismatches in renal transplantation: is the increased failure rate caused by noncytotoxic HLA-DR alloantibodies?
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132-0001, USA.
authors.forename: A
authors.initials: A
authors.lastname: Fuller
authors.forename: T
authors.initials: T
authors.lastname: Profaizer
authors.forename: L
authors.initials: L
authors.lastname: Roberts
authors.forename: T C
authors.initials: TC
authors.lastname: Fuller
mesh_terms: D000918:Antibody Specificity; D003165:Complement System Proteins / Q000276:immunology; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology*; D006684:HLA-DR Antigens; D006650:Histocompatibility Testing; D006801:Humans; D066298:In Vitro Techniques; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000276:immunology*; D011379:Prognosis; D012086:Reoperation
chemical_list: D006684:HLA-DR Antigens; D007518:Isoantibodies; D003165:Complement System Proteins