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SIGNIFICANCE OF HLA IN HUMAN ISLET TRANSPLANTATION.
T. Mohanakumar, PhD, K. Narayanan, PhD, D. Phelan, BA, B. Olack, N. Benshoff, S. Ramachandran, PhD, D. Brennan, MD, J. Odorico, MD, N. Desai, MD and K. Polonsky, MD. Washington Univ. Surg; Washington Univ. Path; St. Louis MO, Washington Univ., Int Med; St. Louis MO, USA, Barnes Hospital, HLA Lab and Madison WI, USA, Univ of Wisconsin, Surg.

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With improvements in isolation and immunosuppression, cellular transplantation (Tx) is becoming a reality. A general belief is that HLA plays only a minimal role in islet Tx. Our goals were; 1) determine the impact of HLA presensitization and islet function, and 2) determine whether post Tx monitoring for antibodies (Abs) to HLA can indicate rejection. Results: 7 recipients JDRF (4) and NIH/ICR (3) were assessed. One patient (Pt) had 3 islet Txs, 3 had 2, and 3 had 1. HLA matching was not done. Cytotoxicity and ELISA identified 1 Pt (JDRF 4) reactive to a panel. FLOW revealed 2 other sensitized Pts (JDRF1 and ICR2). Cytotoxicity crossmatch failed to detect any reactivity to the donors whereas FLOW identified 3 (JDRF1, JDRF3 and ICR2). Two of these (JDRF1 and ICR2) had sensitization only by FLOW and lost islet function within weeks. The third (JDRF4) who was sensitized but negative crossmatch lost islet function. Analysis revealed the presence of a cross-reactive antigen (HLA-B7). ELISPOT for IFN-γ following donor stimulation confirmed cellular sensitization in every case where Ab was defined by FLOW. Donor specific Ab following Tx showed that 2 Pts Tx'd with a negative crossmatch who lost function developed HLA Abs. In summary, cellular Tx follows the same rules as solid organ, ie, pre-existing donor specific HLA Abs are harmful and rejection of the islets is often preceded by the development of HLA Abs. These results have led us to use a positive crossmatch as a contraindication for Tx and to monitor for donor specific HLA Abs to predict islet rejection.