Differences in Baseline Lymphocyte Counts and Autoreactivity are associated with Differences in Outcome of Islet Cell Transplantation in Type 1 Diabetic Patients
- Robert Hilbrands1,7,
- Volkert AL Huurman3,7,
- Pieter Gillard1,4,7,
- Jurjen HL Velthuis3,7,
- Marc De Waele1,
- Chantal Mathieu4,7,
- Leonard Kaufman2,
- Miriam Pipeleers-Marichal1,
- Zhidong Ling1,7,
- Babak Movahedi1,7,
- Daniel Jacobs-Tulleneers-Thevissen1,7,
- Diethard Monbaliu5,
- Dirk Ysebaert6,
- Frans K Gorus1,7,
- Bart O Roep3,7,
- Daniel G Pipeleers1,7 and
- Bart Keymeulen (Bart.Keymeulen{at}uzbrussel.be)1,7
- 1 Diabetes Research Center and UZ Brussel
- 2Department of Biostatistics, Brussels Free University-VUB, Brussels, Belgium
- 3Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands
- 4Department of Endocrinology
- 5Department of Surgery, Universitair Ziekenhuis Gasthuisberg, Catholic University of Leuven-KUL, Belgium
- 6Department of Surgery, Universitair Ziekenhuis Antwerpen, University of Antwerp, Belgium
- 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
- Copyright © American Diabetes Association











