title: Predictive factors of allosensitization after immunosuppressant withdrawal in recipients of long-term cultured islet cell grafts.
abstract: 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 β-cell purity; use of steroids reduced de novo positivity for Luminex class I antibodies.
  
  
  CONCLUSIONS
  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 β-cell purity.
authors.affiliation: Diabetes Research Center and Universitair Ziekenhuis Brussel, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Robert
authors.initials: R
authors.lastname: Hilbrands
authors.forename: Pieter
authors.initials: P
authors.lastname: Gillard
authors.forename: Cornelis R
authors.initials: CR
authors.lastname: Van der Torren
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Ling
authors.forename: Sonja
authors.initials: S
authors.lastname: Verheyden
authors.forename: Daniel
authors.initials: D
authors.lastname: Jacobs-Tulleneers-Thevissen
authors.forename: Bart O
authors.initials: BO
authors.lastname: Roep
authors.forename: Frans H J
authors.initials: FH
authors.lastname: Claas
authors.forename: Christian
authors.initials: C
authors.lastname: Demanet
authors.forename: Frans K
authors.initials: FK
authors.lastname: Gorus
authors.forename: Daniel
authors.initials: D
authors.lastname: Pipeleers
authors.forename: Bart
authors.initials: B
authors.lastname: Keymeulen
mesh_terms: D000328:Adult; D000961:Antilymphocyte Serum / Q000276:immunology; D065095:Calcineurin Inhibitors; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000276:immunology / Q000601:surgery*; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000453:epidemiology; D006085:Graft Survival / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D007519:Isoantigens / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D011237:Predictive Value of Tests; D016036:Seroepidemiologic Studies; D013375:Substance Withdrawal Syndrome / Q000276:immunology*; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000961:Antilymphocyte Serum; D065095:Calcineurin Inhibitors; D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D007519:Isoantigens; D009173:Mycophenolic Acid; D016559:Tacrolimus; D008775:Methylprednisolone