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Differences in Baseline Lymphocyte Counts and Autoreactivity are associated with Differences in Outcome of Islet Cell Transplantation in Type 1 Diabetic Patients

  1. Robert Hilbrands1,7,
  2. Volkert AL Huurman3,7,
  3. Pieter Gillard1,4,7,
  4. Jurjen HL Velthuis3,7,
  5. Marc De Waele1,
  6. Chantal Mathieu4,7,
  7. Leonard Kaufman2,
  8. Miriam Pipeleers-Marichal1,
  9. Zhidong Ling1,7,
  10. Babak Movahedi1,7,
  11. Daniel Jacobs-Tulleneers-Thevissen1,7,
  12. Diethard Monbaliu5,
  13. Dirk Ysebaert6,
  14. Frans K Gorus1,7,
  15. Bart O Roep3,7,
  16. Daniel G Pipeleers1,7 and
  17. Bart Keymeulen (Bart.Keymeulen{at}uzbrussel.be)1,7
  1. 1 Diabetes Research Center and UZ Brussel
  2. 2Department of Biostatistics, Brussels Free University-VUB, Brussels, Belgium
  3. 3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
  4. 4Department of Endocrinology
  5. 5Department of Surgery, Universitair Ziekenhuis Gasthuisberg, Catholic University of Leuven-KUL, Belgium
  6. 6Department of Surgery, Universitair Ziekenhuis Antwerpen, University of Antwerp, Belgium
  7. 7Juvenile Diabetes Research Foundation Center for Beta Cell Therapy in Diabetes

    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.

    Research design and Methods: Thirty non-uremic 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 post transplant (PT) months, ie 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-lymphocytes, as well as a T-cell autoreactivity against IA2 and/or GAD. In one of them a liver biopsy during PT year 2 showed B-lymphocyte 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.

    Conclusion: Higher total and B-lymphocyte 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-MMF 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.

    Footnotes

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