PMID- 17456201 OWN - NLM STAT- MEDLINE DCOM- 20070807 LR - 20230124 IS - 1600-6135 (Print) IS - 1600-6135 (Linking) VI - 7 IP - 5 DP - 2007 May TI - Pretransplant HLA antibodies are associated with reduced graft survival after clinical islet transplantation. PG - 1242-8 AB - Despite significant improvements in islet transplantation, long-term graft function is still not optimal. It is likely that both immune and nonimmune factors are involved in the deterioration of islet function over time. Historically, the pretransplant T-cell crossmatch and antibody screening were done by anti-human globulin--complement-dependent cytotoxicity (AHG-CDC). Class II antibodies were not evaluated. In 2003, we introduced solid-phase antibody screening using flow-based beads and flow crossmatching. We were interested to know whether pretransplant human leukocyte antigen (HLA) antibodies or a positive flow crossmatch impacted islet function post-transplant. A total of 152 islet transplants was performed in 81 patients. Islet function was determined by a positive C-peptide. Results were analyzed by procedure. Class I and class II panel reactive antibody (PRA) > 15% and donor-specific antibodies (DSA) were associated with a reduced C-peptide survival (p<0.0001 and p<0.0001, respectively). A positive T- and or B-cell crossmatch alone was not. Pretransplant HLA antibodies detectable by flow beads are associated with reduced graft survival. This suggests that the sirolimus and low-dose tacrolimus-based immunosuppression may not control the alloimmune response in this presensitized population and individuals with a PRA > 15% may require more aggressive inductive and maintenance immunosuppression, or represent a group that may not benefit from islet transplantation. FAU - Campbell, P M AU - Campbell PM AD - Department of Medicine, Division of Nephrology and Immunology, University of Alberta, Capital Health, Edmonton, Alberta, Canada. trish.campbell@ualberta.ca FAU - Salam, A AU - Salam A FAU - Ryan, E A AU - Ryan EA FAU - Senior, P AU - Senior P FAU - Paty, B W AU - Paty BW FAU - Bigam, D AU - Bigam D FAU - McCready, T AU - McCready T FAU - Halpin, A AU - Halpin A FAU - Imes, S AU - Imes S FAU - Al Saif, F AU - Al Saif F FAU - Lakey, J R T AU - Lakey JR FAU - Shapiro, A M J AU - Shapiro AM LA - eng GR - DK59101/DK/NIDDK NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Transplant JT - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JID - 100968638 RN - 0 (Antibodies) RN - 0 (Antilymphocyte Serum) RN - 0 (C-Peptide) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Immunosuppressive Agents) RN - W36ZG6FT64 (Sirolimus) RN - WM0HAQ4WNM (Tacrolimus) SB - IM MH - Adult MH - Antibodies/*immunology MH - Antilymphocyte Serum/therapeutic use MH - B-Lymphocytes/immunology/pathology MH - C-Peptide/metabolism MH - Female MH - Graft Rejection/prevention & control MH - Graft Survival/*immunology MH - Histocompatibility Antigens Class I/*immunology MH - Histocompatibility Antigens Class II/*immunology MH - Histocompatibility Testing MH - Humans MH - Immunosuppressive Agents/therapeutic use MH - Islets of Langerhans/immunology/metabolism MH - Islets of Langerhans Transplantation/*immunology/pathology MH - Male MH - Proportional Hazards Models MH - Sirolimus/therapeutic use MH - T-Lymphocytes/immunology/pathology MH - Tacrolimus/therapeutic use MH - Treatment Outcome EDAT- 2007/04/26 09:00 MHDA- 2007/08/08 09:00 CRDT- 2007/04/26 09:00 PHST- 2007/04/26 09:00 [pubmed] PHST- 2007/08/08 09:00 [medline] PHST- 2007/04/26 09:00 [entrez] AID - S1600-6135(22)02732-0 [pii] AID - 10.1111/j.1600-6143.2007.01777.x [doi] PST - ppublish SO - Am J Transplant. 2007 May;7(5):1242-8. doi: 10.1111/j.1600-6143.2007.01777.x.