PMID- 16916655 OWN - NLM STAT- MEDLINE DCOM- 20061222 LR - 20071203 IS - 0198-8859 (Print) IS - 0198-8859 (Linking) VI - 67 IP - 8 DP - 2006 Aug TI - Alloantibodies and the outcome of cadaver kidney allografts. PG - 597-604 AB - 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. FAU - Vasilescu, Elena Rodica AU - Vasilescu ER AD - Department of Pathology, Columbia University, New York, NY, USA. FAU - Ho, Eric K AU - Ho EK FAU - Colovai, Adriana I AU - Colovai AI FAU - Vlad, George AU - Vlad G FAU - Foca-Rodi, Aurica AU - Foca-Rodi A FAU - Markowitz, Glen S AU - Markowitz GS FAU - D'Agati, Vivette AU - D'Agati V FAU - Hardy, Mark A AU - Hardy MA FAU - Ratner, Lloyd E AU - Ratner LE FAU - Suciu-Foca, Nicole AU - Suciu-Foca N LA - eng GR - AI055234-03/AI/NIAID NIH HHS/United States GR - AI25210-19A/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20060523 PL - United States TA - Hum Immunol JT - Human immunology JID - 8010936 RN - 0 (Isoantibodies) SB - IM MH - Cadaver MH - Female MH - Graft Rejection/immunology MH - Humans MH - Isoantibodies/*blood MH - Kidney Transplantation/*immunology MH - Male MH - Tissue Donors MH - Transplantation, Homologous/*immunology EDAT- 2006/08/19 09:00 MHDA- 2006/12/23 09:00 CRDT- 2006/08/19 09:00 PHST- 2006/02/10 00:00 [received] PHST- 2006/08/19 09:00 [pubmed] PHST- 2006/12/23 09:00 [medline] PHST- 2006/08/19 09:00 [entrez] AID - S0198-8859(06)00105-4 [pii] AID - 10.1016/j.humimm.2006.04.012 [doi] PST - ppublish SO - Hum Immunol. 2006 Aug;67(8):597-604. doi: 10.1016/j.humimm.2006.04.012. Epub 2006 May 23.