Recurrence of Type 1 Diabetes After Simultaneous Pancreas-Kidney Transplantation, Despite Immunosuppression, Is Associated With Autoantibodies and Pathogenic Autoreactive CD4 T-Cells

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FIG. 2.
FIG. 2.

Clinical course, autoimmunity assessment, and biopsy in patient 2. Patient 2 is a Caucasian female (HLA A2/A24, B44/B56, DR5/DR9) who developed type 1 diabetes at age 8 years. She received an SPK transplant from an HLA A2/A3, B7/B14, DR7/DR9 donor at age 30 years. Her pancreas transplant successfully reversed diabetes. After approximately 9 years, the patient developed hyperglycemia requiring insulin therapy, while the function of the kidney and exocrine pancreas allografts remained unchanged. A: Autoantibody levels before transplant and on follow-up. The patient converted to GAD and IA-2 autoantibody positivity 6 years after transplantation. Hyperglycemia ensued 3.5 years after autoantibody conversion. B: Pancreas transplant biopsy stained as labeled, obtained ∼7 months after the recurrence of hyperglycemia. There was evidence for insulitis and β-cell loss. C: C-peptide levels from the time of hyperglycemia recurrence and % of IGRP tetramer–positive T-cells in the CD8 T-cell population. The horizontal blue line represents the cutoff of the T-cell assay (0.1%). Percentage of cells plotted is the specific staining value shown in D minus the background staining with control peptide. Circulating CD8 T-cells reacting against IGRP were found in a sample obtained at the time of biopsy and again ∼1 year after treatment. D: Flow cytometry plots showing IGRP-specific autoreactive CD8 T-cells. Staining with tetramers loaded with a control peptide yielded 0.1% background staining levels, gating on PBMC (not shown). The numbers above the plots identify the IGRP T-cell measurements in C, thus corresponding to the samples measured closest to the onset of hyperglycemia and over 1 year after treatment. DM, diabetes; Tx, treatment. (A high-quality digital representation of this figure is available in the online issue.)

This Article

  1. Diabetes vol. 59 no. 4 947-957