Repeat donor HLA-DR mismatches in renal transplantation: is the increased failure rate caused by noncytotoxic HLA-DR alloantibodies?
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.
Fuller
A
A
Department of Pathology, University of Utah School of Medicine, Salt Lake City 84132-0001, USA.
Profaizer
T
T
Roberts
L
L
Fuller
T C
TC
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
D006684:HLA-DR Antigens; D007518:Isoantibodies; D003165:Complement System Proteins