Differences in baseline lymphocyte counts and autoreactivity are associated with differences in outcome of islet cell transplantation in type 1 diabetic patients
R Hilbrands, VAL Huurman, P Gillard, JHL Velthuis… - Diabetes, 2009 - Am Diabetes Assoc
Diabetes, 2009•Am Diabetes Assoc
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 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 …
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 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 …
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 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 β-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.
Am Diabetes Assoc