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.

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 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.

FIG. 1.

T- and B-cell count at baseline and during 6 months after transplantation (A) in islet graft recipients gaining insulin independence (solid line) and remaining insulin independent (dotted line). Data represent means ± SE; *P < 0.05. B: Gain of insulin independence according to baseline in vitro T-cell reactivity against islet autoantigens. The lower panel shows gain of insulin independence in three different groups according to both T-cell autoreactivity and baseline B-cell count.

FIG. 2.

The effect of baseline total lymphocyte count (A), in vitro T-cell reactivity against islet autoantigens or both (B) on glycemic stability and C-peptide release.

FIG. 3.

Two islets were identified in the portal tract. Semiconsecutive sections of islet two show inflammatory cells located around the graft, which are dominated by CD20+ B-cells. (A high-quality digital representation of this figure is available in the online issue.)