title: Alloantibodies and the outcome of cadaver kidney allografts.
abstract: The role of humoral immunity in causing antibody-mediated rejection (AMR) of organ allografts has been extensively documented. For this reason, negative complement-dependent cytotoxicity (CDC) cross-matches between recipient sera and donor T and B lymphocytes have become a mandatory requirement for cadaveric kidney transplantation. However, the significance of donor-specific antibodies (DSAs) detectable only by flow cytometry (FC) or solid phase assays (SPA) but not CDC is still controversial. We have performed a retrospective analysis of FC cross-matching results in 80 consecutive cadaver kidney allograft recipients. Antibodies against HLA class I and class II antigens were measured by CDC and SPA in sequential samples of sera obtained prior to transplantation. The preoperative cross-match was performed by CDC using magnetically sorted T and B cells from donor spleen. Sera obtained from each patient before and at the time of transplantation were included in the final cross-match. The sample of serum obtained at the time of transplantation was cross-matched retrospectively by FC and analyzed for anti-HLA antibody specificity on high resolution SPA. The actuarial kidney allograft survival at one year was 98%. Two of these eighty patients lost the graft, one due to AMR, the other for reasons unrelated to DSAs. Donor-specific antibodies were detected by FC in 17 of 80 patients, yet only 6 of 17 had an early episode of AMR. This episode was successfully reversed by desensitization therapy using intravenous immunoglobin (IVIG) and plasmapheresis. Flow cytomery cross-matching showed 95% specificity but only 35% sensitivity for prediction of AMR (p = 0.002). There was a significant correlation between high panel reactive antibodies (PRA) and positive FC cross-matching (p = 0 .0001), as well as high PRA and AMR (p = 0.0004 by CDC and 0.0011 by Luminex). Reversible AMR occurred 12-30 days post-transplantation in 8 patients. Of these 8 patients, 3 had no detectable DSAs in spite of C4d positivity, 4 had C4d deposition in conjunction with anti-HLA antibodies, and 1 patient had DSAs (anti-MICA) yet no C4d deposition. We conclude that early initiation of desensitization protocols can prevent transplant failure and that retrospective FC cross-matches may facilitate the diagnosis of AMR. Extensive analysis of patients' sera using a comprehensive set of tests may contribute to early treatment and better understanding of the mechanism underlying humoral rejection.
authors.affiliation: Department of Pathology, Columbia University, New York, NY, USA.
authors.forename: Elena Rodica
authors.initials: ER
authors.lastname: Vasilescu
authors.forename: Eric K
authors.initials: EK
authors.lastname: Ho
authors.forename: Adriana I
authors.initials: AI
authors.lastname: Colovai
authors.forename: George
authors.initials: G
authors.lastname: Vlad
authors.forename: Aurica
authors.initials: A
authors.lastname: Foca-Rodi
authors.forename: Glen S
authors.initials: GS
authors.lastname: Markowitz
authors.forename: Vivette
authors.initials: V
authors.lastname: D'Agati
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hardy
authors.forename: Lloyd E
authors.initials: LE
authors.lastname: Ratner
authors.forename: Nicole
authors.initials: N
authors.lastname: Suciu-Foca
mesh_terms: D002102:Cadaver; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D014019:Tissue Donors; D014184:Transplantation, Homologous / Q000276:immunology*
chemical_list: D007518:Isoantibodies