Previously accepted bet a cells of langerhans are rejected if both stimuli are presented on the same cell

Previously accepted bet a cells of langerhans are rejected if both stimuli are presented on the same cell

13 Abstracts 6.3 THE IMPACT OF HLA MATCHING AND RACE ON LONG-TERM CARDIAC SURVIVAL. MH Park, DE Tolman, T Saad, D Craft, D Dean, PM KimbalL Divisio...

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Abstracts

6.3

THE IMPACT OF HLA MATCHING AND RACE ON LONG-TERM CARDIAC SURVIVAL. MH Park, DE Tolman, T Saad, D Craft, D Dean, PM KimbalL Division of Cardiology, Medical College of Virginia, Richmond, Virginia. This retrospective analysis examines the impact of recipient race as well as HLA matching upon long-term survival following heart transplantation. We analyzed 336 males (77% Caucasians (Cauc) ; 23% African-Americans (AA» transplanted between 1983 and 1994 receiving cyclosporine-based immunosuppression. HLA matching was defined as poor for 0 antigens matched, moderate for s:; 2 AB or I DR matched and well for;:: 3 AB or 2 DR matched. The overall survival among AA was lower than Cauc. Survival at 1,5 and 9 years was 83%, 63%, and 46% for Cauc versus 70%, 51%, and 32% for AA (p=0.05). Furthermore, AA received more poorly matched organs compared to Cauc. Matching for Class I among Cauc showed 46%, 53% and 1% received poor, moderate and well matched hearts. In contrast, AA received 65%, 33% and 0% poor, moderate or well matched hearts (p=0.03). An analysis of Class II data revealed the same pattern: 63%,35% and 2% ofCauc versus 78%, 18% and 4% of AA received poor, moderate or well matched hearts (p=0.04). Cauc survival improved when moderately versus poorly matched for Class I. The 5 year survival rate was 65% vs 58% when moderately versus poorly matched (p=0.06). Well matched Cauc (n=3) showed 100% long-term survival. In contrast, Class II matching did not have an effect. Five year survival among Cauc was 62% and 58% when moderately or poorly matched (p>O.l). AA showed a trend towards improved survival when moderately versus poorly matched for Class I (5 year rates of 64% versus 47%, p>O.l). Class II matching showed no benefit towards survival with 5 year rates of 63% and 54% for moderate versus poorly matched hearts (p>O.l). When comparing equivalent degrees of matching, AA demonstrated a trend towards inferior survival when poorly-matched for Class I relative to Cauc. Survival at 5 years was 58% for Cauc and 47% for AA (p=0.09). Analysis for Class II poorly matched patients showed no difference with 5 year rates of 58% and 54% for Cauc and AA (p>O.l). No racial disparity was observed for moderate matched Class I or Class II analysis. The 5 year rates for Cauc and AA were 66% and 64% for Class I and 62% and 63% for Class II (p>O.I). In summary, our study showed AA survival was inferior to Cauc; matching for Class I had a modest impact on long-term survival although the degree of impact differed between the two groups. Since AA received disproportionately more poorly-matched oragans, they were denied this immunologically advantage which may partially account for the survival difference.

6.3

PREVIOUSL Y ACCEPTED BETA CELLS OF LANGERHANS ARE REJECTED IF BOTH STIMULI ARE PRESENTED ON THE SAME CELL. Vera Hauptfeld, Paul E. Lacy, Ralph 1. Graff, Jonathan Yoken and Chris Tullis. Department of Surgery, Saint Louis University and Department of Pathology, Washington University, Saint Louis, MO. Streptozotocin-induced diabetes in mice can be reversed by transplantation of allogeneic islets of Langerhans whose APCs have been eliminated by anti-class II antibody and complement prior to transplantation. The purpose of this study was to determine the genetic requirements for interaction between class I and class II molecules in the initiation of rejection of previously accepted islet cell allografts. C57BLl6 mice were injected with a tolerogenic dose of donor red blood cells prior to induction of diabetes. They were made normoglycemic by implantation of class II-depleted dispersed BIO.BR islet cells. At 21 days, normoglycemic, allograft-bearing animals were challenged with injections of splenocytes from mice with various intra-H-2 recombinant haplotypes which were selected to share different regions of the H-2 complex with the accepted BIO.BR islet allografts. Cells from strains not syngeneic with class I antigens of the islet donor strain did not initiate islet cell rejection, regardless of the genotype of class II antigens they expressed. Cells from all strains which shared at least one class I antigen with the islet cell graft initiated the immune response against the grafted islets as long as class II antigens were also present. The class II antigens could be of any origin, including that of the host. The rejection was not initiated by the injection of cells bearing donor class I antigens if the class II antigens were absent.