Posttransplantation production of donor HLA-specific antibodies as a predictor of renal transplant outcome.
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.
Worthington
Judith E
JE
Transplantation Laboratory, Manchester Institute of Nephrology and Transplantation, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL, UK. jworth@mint.cmht.nwest.nhs.uk
Martin
Susan
S
Al-Husseini
Dalia M
DM
Dyer
Philip A
PA
Johnson
Robert W G
RW
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
D000906:Antibodies; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007518:Isoantibodies