Differences in Baseline Lymphocyte Counts and Autoreactivity are associated with Differences in Outcome of Islet Cell Transplantation in Type 1 Diabetic Patients
Hilbrands, Robert × Huurman, Volkert Al Gillard, Pieter Velthuis, Jurjen Hl De Waele, Marc Mathieu, Chantal Kaufman, Leonard Pipeleers-Marichal, Miriam Ling, Zhidong Movahedi, Babak Jacobs-Tulleneers-Thevissen, Daniel Monbaliu, Diethard Ysebaert, Dirk Gorus, Frans K Roep, Bart O Pipeleers, Daniel G Keymeulen, Bart #
Transplant International vol:22 pages:46
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.