PMID- 23857001 OWN - NLM STAT- MEDLINE DCOM- 20130923 LR - 20161125 IS - 1534-6080 (Electronic) IS - 0041-1337 (Linking) VI - 96 IP - 2 DP - 2013 Jul 27 TI - Predictive factors of allosensitization after immunosuppressant withdrawal in recipients of long-term cultured islet cell grafts. PG - 162-9 LID - 10.1097/TP.0b013e3182977afc [doi] AB - BACKGROUND: Islet transplantation has been reported to induce allosensitization in the majority of type 1 diabetic recipients of fresh or shortly incubated islet grafts prepared from one to three donors. METHODS: We examined the appearance of human leukocyte antigen (HLA) antibodies after withdrawal of immunosuppressants in 35 type 1 diabetic recipients of islet cell grafts prepared from a median of 6 donors (range, 2-11), cultured for longer periods, and characterized for their cellular composition. Immunosuppression consisted of antithymocyte globulin induction followed by mycophenolate mofetil plus calcineurin inhibitors (n=28, with 7 also receiving steroids) or sirolimus with (n=3) or without calcineurin inhibitors (n=4). Both the complement-dependent cytotoxicity (CDC) assay (class I) and the solid-phase flow-based Luminex method (class I and II) were used to identify HLA antibodies. RESULTS: Immunosuppressant withdrawal resulted in CDC positivity for class I antibodies in only 6% of patients. However, the majority became positive for class I antibodies (72%) or class II antibodies (72%) in the Luminex assay; positivity was not correlated to a higher number of donors or HLA mismatches, but with a lower beta-cell purity; use of steroids reduced de novo positivity for Luminex class I antibodies. CONCLUSION: Allosensitization to cultured human islet cell grafts was low when assessed by CDC assay but high in Luminex. No correlation was found with the number of donors but risk was higher for grafts with lower beta-cell purity. FAU - Hilbrands, Robert AU - Hilbrands R AD - Diabetes Research Center and Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium. FAU - Gillard, Pieter AU - Gillard P FAU - Van der Torren, Cornelis R AU - Van der Torren CR FAU - Ling, Zhidong AU - Ling Z FAU - Verheyden, Sonja AU - Verheyden S FAU - Jacobs-Tulleneers-Thevissen, Daniel AU - Jacobs-Tulleneers-Thevissen D FAU - Roep, Bart O AU - Roep BO FAU - Claas, Frans H J AU - Claas FH FAU - Demanet, Christian AU - Demanet C FAU - Gorus, Frans K AU - Gorus FK FAU - Pipeleers, Daniel AU - Pipeleers D FAU - Keymeulen, Bart AU - Keymeulen B LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Transplantation JT - Transplantation JID - 0132144 RN - 0 (Antilymphocyte Serum) RN - 0 (Calcineurin Inhibitors) RN - 0 (Histocompatibility Antigens Class I) RN - 0 (Immunosuppressive Agents) RN - 0 (Isoantibodies) RN - 0 (Isoantigens) RN - HU9DX48N0T (Mycophenolic Acid) RN - WM0HAQ4WNM (Tacrolimus) RN - X4W7ZR7023 (Methylprednisolone) SB - IM MH - Adult MH - Antilymphocyte Serum/immunology MH - Calcineurin Inhibitors MH - Cells, Cultured MH - Cytotoxicity Tests, Immunologic MH - Diabetes Mellitus, Type 1/epidemiology/immunology/*surgery MH - Female MH - Graft Rejection/*drug therapy/epidemiology MH - Graft Survival/immunology MH - Histocompatibility Antigens Class I/immunology MH - Humans MH - Immunosuppressive Agents/*administration & dosage/*adverse effects MH - Islets of Langerhans Transplantation/*immunology MH - Isoantibodies/blood/immunology MH - Isoantigens/immunology MH - Male MH - Methylprednisolone/administration & dosage/adverse effects MH - Middle Aged MH - Mycophenolic Acid/administration & dosage/adverse effects/analogs & derivatives MH - Predictive Value of Tests MH - Seroepidemiologic Studies MH - Substance Withdrawal Syndrome/*immunology MH - Tacrolimus/administration & dosage/adverse effects EDAT- 2013/07/17 06:00 MHDA- 2013/09/24 06:00 CRDT- 2013/07/17 06:00 PHST- 2013/07/17 06:00 [entrez] PHST- 2013/07/17 06:00 [pubmed] PHST- 2013/09/24 06:00 [medline] AID - 00007890-201307270-00009 [pii] AID - 10.1097/TP.0b013e3182977afc [doi] PST - ppublish SO - Transplantation. 2013 Jul 27;96(2):162-9. doi: 10.1097/TP.0b013e3182977afc.