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Anti-MHC antibodies in a murine model of islet transplantation
S8
Abstracts
1.03 9-OR ANTI-MHC ANTIBODIES IN A MURINE MODEL OF ISLET TRANSPLANTATION. Jeremy Goodman, Niraj Desai, Nicholas Benshoff, Wei Lu, William C. Chapman, T. Mohanakumar. Department of Surgery, Washington University School of Medicine, Saint Louis, MO Introduction: Recent successes in islet transplantation have renewed interest in this therapy. The impact of prior sensitization to MHC antigens in islet transplantation has not been addressed, and pretransplant crossmatching is not routinely performed. The purpose of this study was to define the role of anti-MHC antibodies in a murine model of islet transplantation. Methods: BALB/c mice (H2d) were used as donors for C57BL/6 recipients (H2b). Recipients were sensitized by two weekly IP injections of 107 BALB/c splenocytes. Antibody development was confirmed by flow cytometry. Recipients were rendered diabetic with streptozotocin, IP. Islets were harvested from BALB/c pancreata by collagenase digestion and Ficoll separation. Five hundred islets were transplanted into sensitized (n⫽25) and non-sensitized (control, n⫽8) mice. Blood glucose was measured daily, and rejection was defined as the first day of persistent levels above 200 mg/dl. Results: All mice undergoing the sensitization regimen produced anti-H2d antibodies. Control mice had no antibodies. Sensitized recipients rejected islets at a median of 1 day, while control mice rejected at a median of 14 days (p⬍0.0001). Only 3 of 25 sensitized mice maintained normoglycemia beyond 3 days. Posttransplant, all mice demonstrated anti-H2d antibodies. Conclusions: Islets were susceptible to hyperacute rejection. Pretransplant sensitization prevented successful transplantation in the majority of recipients. Further, control animals demonstrated de novo antibody development following transplantation. These findings suggest that pretransplant sensitization to MHC and de novo anti-MHC antibody development may play a role in islet cell rejection. Therefore, consideration should be given to crossmatching prior to clinical transplantation.
Abstracts
1.03 9-OR ANTI-MHC ANTIBODIES IN A MURINE MODEL OF ISLET TRANSPLANTATION. Jeremy Goodman, Niraj Desai, Nicholas Benshoff, Wei Lu, William C. Chapman, T. Mohanakumar. Department of Surgery, Washington University School of Medicine, Saint Louis, MO Introduction: Recent successes in islet transplantation have renewed interest in this therapy. The impact of prior sensitization to MHC antigens in islet transplantation has not been addressed, and pretransplant crossmatching is not routinely performed. The purpose of this study was to define the role of anti-MHC antibodies in a murine model of islet transplantation. Methods: BALB/c mice (H2d) were used as donors for C57BL/6 recipients (H2b). Recipients were sensitized by two weekly IP injections of 107 BALB/c splenocytes. Antibody development was confirmed by flow cytometry. Recipients were rendered diabetic with streptozotocin, IP. Islets were harvested from BALB/c pancreata by collagenase digestion and Ficoll separation. Five hundred islets were transplanted into sensitized (n⫽25) and non-sensitized (control, n⫽8) mice. Blood glucose was measured daily, and rejection was defined as the first day of persistent levels above 200 mg/dl. Results: All mice undergoing the sensitization regimen produced anti-H2d antibodies. Control mice had no antibodies. Sensitized recipients rejected islets at a median of 1 day, while control mice rejected at a median of 14 days (p⬍0.0001). Only 3 of 25 sensitized mice maintained normoglycemia beyond 3 days. Posttransplant, all mice demonstrated anti-H2d antibodies. Conclusions: Islets were susceptible to hyperacute rejection. Pretransplant sensitization prevented successful transplantation in the majority of recipients. Further, control animals demonstrated de novo antibody development following transplantation. These findings suggest that pretransplant sensitization to MHC and de novo anti-MHC antibody development may play a role in islet cell rejection. Therefore, consideration should be given to crossmatching prior to clinical transplantation.