PRESENCE OF DONOR ANTIGEN-REACTIVE HLA ANTIBODIES DETECTED BY FLOW CYTOMETRY IDENTIFY RENAL PATIENTS AT HIGH RISK FOR POOR GRAFT OUTCOME.
NL Reinsmoen, FE Ward, E Tuttle-Newhall, S Peplinski, A Clark, S Kaestner and R Bollinger, Departments of Pathology and Surgery, Duke University Medical Center & Health System, Durham, NC.
Current immunotherapy protocols have become effective in limiting the incidence of acute cellular rejection (ACR) in kidney transplantation; however, chronic rejection (CR) continues to affect long-term graft survival. While cytotoxic crossmatches (CDC-AHG) have allowed centers to limit hyperacute rejection, the more sensitive flow cytometric crossmatch may help identify recipients at high risk for ACR and CR. To determine if the presence of anti-donor HLA specific antibodies detected by flow cytometry, but not detectable by cytotoxicity, could predict poor graft outcome, we preformed the following retrospective analysis. During the period of 1-90 to 3-99, 729 HLA non-identical renal transplants with negative CDC crossmatch were performed at our center. We identified recipients who had poor graft outcome as evidenced by CR or graft loss. We also included recipients who had experienced 1 or more AR episodes and thus were at high risk for developing CR (n=229). We tested the sera used for the final crossmatch by flow cytometry PRA bead assay to identify class I vs class II-directed antibodies. No anti-HLA antibodies were detected by either method for 67% of the sera, and anti-HLA antibodies were detected by both methods for 20% of the sera. Anti-HLA antibodies were detected by flow but not by CDC-AHG for 13% of the sera, which were then tested by the flow cytometry specificity bead assay. Sera from 18 recipients were identified to have antibodies reactive with donor class I, class II or both antigens. The clinical outcome was compared for these 18 recipients and the 211 poor graft outcome recipients. In comparison to the poor outcome group, the donor antigen specific group had a shorter time to first AR (2 vs 3.4 mo), a shorter time to CR (15.4 vs 21 mo), and a higher graft loss (50% vs 28%) although due to the study size, the p values did not reach statistical significance. It appears from this data that donor antigen-reactive anti-HLA antibodies detectable by flow, but not by CDC-AHG, are a useful predictor of immune complications and a poor graft outcome.