title: Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome.
abstract: BACKGROUND
  This study aimed to determine whether the production, in renal transplant recipients, of antibodies directed against donor HLA mismatches is predictive of transplant failure.
  
  
  METHODS
  The failure study group comprised 112 adult recipients of primary renal transplants who had re-entered the transplant waiting list after failure of the first graft. A control group of 123 recipients with functioning transplants was selected from transplantations performed during the same time period, in which patients had equivalent HLA matching and immunosuppression and a minimum of 5 years of follow-up. Sera taken before transplantation and at 1, 3, and 6 months and annually after transplantation were tested by enzyme-linked immunoabsorbent assay (ELISA) for the presence of HLA class I- and class II-specific antibodies. Antibody specificity was defined by a combination of cytotoxicity, ELISA, and flow cytometry techniques to determine whether the antibodies were directed against donor mismatches.
  
  
  RESULTS
  All recipients were negative for donor HLA-specific antibodies before transplantation. After transplantation, 57 (50.9%) of the 112 patients in the failure group produced donor HLA-specific antibodies compared with 2 (1.6%) of the 123 controls (P<0.0001; odds ratio [OR]=64.98; confidence interval [CI], 14.78-399.51). For 60% of the donor-specific antibody-positive patients, antibodies were detected before transplant failure. In 17 cases, these were class I specific; in 14 cases, class II specific; and in 3 cases, specific for both class I and II.
  
  
  CONCLUSIONS
  This study has demonstrated that the production of posttransplantation antibodies directed against donor HLA-A, -B, -Cw, -DR, and -DQ mismatches are all strongly predictive of transplant failure.
authors.affiliation: Transplantation Laboratory, Manchester Institute of Nephrology and Transplantation, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK. jworth@mint.cmht.nwest.nhs.uk
authors.forename: Judith E
authors.initials: JE
authors.lastname: Worthington
authors.forename: Susan
authors.initials: S
authors.lastname: Martin
authors.forename: Dalia M
authors.initials: DM
authors.lastname: Al-Husseini
authors.forename: Philip A
authors.initials: PA
authors.lastname: Dyer
authors.forename: Robert W G
authors.initials: RW
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000906:Antibodies / Q000032:analysis; D000917:Antibody Formation; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000378:metabolism*; D016030:Kidney Transplantation / Q000276:immunology*; D011184:Postoperative Period; D011379:Prognosis; D014019:Tissue Donors; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies