title: Differences in baseline lymphocyte counts and autoreactivity are associated with differences in outcome of islet cell transplantation in type 1 diabetic patients.
abstract: OBJECTIVE
  The metabolic outcome of islet cell transplants in type 1 diabetic patients is variable. This retrospective analysis examines whether differences in recipient characteristics at the time of transplantation are correlated with inadequate graft function.
  
  
  METHODS
  Thirty nonuremic C-peptide-negative type 1 diabetic patients had received an intraportal islet cell graft of comparable size under an ATG-tacrolimus-mycophenolate mofetil regimen. Baseline patient characteristics were compared with outcome parameters during the first 6 posttransplant months (i.e., plasma C-peptide, glycemic variability, and gain of insulin independence). Correlations in univariate analysis were further examined in a multivariate model.
  
  
  RESULTS
  Patients that did not become insulin independent exhibited significantly higher counts of B-cells as well as a T-cell autoreactivity against insulinoma-associated protein 2 (IA2) and/or GAD. In one of them, a liver biopsy during posttransplant year 2 showed B-cell accumulations near insulin-positive beta-cell aggregates. Higher baseline total lymphocytes and T-cell autoreactivity were also correlated with lower plasma C-peptide levels and higher glycemic variability.
  
  
  CONCLUSIONS
  Higher total and B-cell counts and presence of T-cell autoreactivity at baseline are independently associated with lower graft function in type 1 diabetic patients receiving intraportal islet cells under ATG-tacrolimus-mycophenolate mofetil therapy. Prospective studies are needed to assess whether control of these characteristics can help increase the function of islet cell grafts during the first year posttransplantation.
authors: Diabetes Research Center and Universitair Ziekenhuis Brussels, Brussels Free University-Vrije Universiteit Brussel (VUB), Brussels, Belgium.
authors: Robert
authors: R
authors: Hilbrands
authors: Volkert A L
authors: VA
authors: Huurman
authors: Pieter
authors: P
authors: Gillard
authors: Jurjen H L
authors: JH
authors: Velthuis
authors: Marc
authors: M
authors: De Waele
authors: Chantal
authors: C
authors: Mathieu
authors: Leonard
authors: L
authors: Kaufman
authors: Miriam
authors: M
authors: Pipeleers-Marichal
authors: Zhidong
authors: Z
authors: Ling
authors: Babak
authors: B
authors: Movahedi
authors: Daniel
authors: D
authors: Jacobs-Tulleneers-Thevissen
authors: Diethard
authors: D
authors: Monbaliu
authors: Dirk
authors: D
authors: Ysebaert
authors: Frans K
authors: FK
authors: Gorus
authors: Bart O
authors: BO
authors: Roep
authors: Daniel G
authors: DG
authors: Pipeleers
authors: Bart
authors: B
authors: Keymeulen
mesh_terms: D000328:Adult; D000925:Anticoagulants / Q000627:therapeutic use; D000961:Antilymphocyte Serum / Q000627:therapeutic use; D001706:Biopsy; D002096:C-Peptide / Q000097:blood / Q000172:deficiency; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000502:physiology*; D016381:Islets of Langerhans Transplantation / Q000276:immunology*; D008099:Liver / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000627:therapeutic use; D012016:Reference Values; D012086:Reoperation / Q000706:statistics & numerical data; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016559:Tacrolimus / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D000961:Antilymphocyte Serum; D002096:C-Peptide; D007166:Immunosuppressive Agents; D007328:Insulin; D009173:Mycophenolic Acid; D016559:Tacrolimus