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Analysis of T-Cell Assays to Measure Autoimmune Responses in Subjects With Type 1 Diabetes

Results of a Blinded Controlled Study

¹ Immune Tolerance Network, Bethesda, Maryland
² Hospital for Sick Children, University of Toronto, Toronto, Canada
³ University of Washington, Seattle, Washington
⁴ Barbara Davis Research Center, University of Colorado, Denver, Colorado
⁵ Benaroya Research Center, Seattle, Washington
⁶ Diabetes Center, University of California at San Francisco, San Francisco, California
⁷ Naomi Berrie Diabetes Center, Columbia University, New York, New York

Address correspondence and reprint requests to Kevan C. Herold MD, College of Physicians and Surgeons, Columbia University, PH8 Rm 864, 630 W. 168th St., New York, NY 10032. E-mail: kh318{at}columbia.edu

Abbreviations: DASP, Diabetes Autoantibody Standardization Program; ELISpot, enzyme-linked immunospot; IA2, insulinoma-associated protein 2; ICA, islet cell antibody; IL, interleukin; ITN, Immune Tolerance Network; MHC, major histocompatibility complex; PBMC, peripheral blood mononuclear cell; ROC, receiver operating characteristic

Type 1 diabetes is a chronic autoimmune disease mediated by autoreactive T-cells. Several experimental therapies targeting T-cells are in clinical trials. To understand how these therapies affect T-cell responses in vivo, assays that directly measure human T-cell function are needed. In a blinded, multicenter, case-controlled study conducted by the Immune Tolerance Network, we tested responses in an immunoblot and T-cell proliferative assay to distinguish type 1 diabetic patients from healthy control subjects. Peripheral blood cells from 39 healthy control subjects selected for DR4 and 23 subjects with recently diagnosed type 1 diabetes were studied. Autoantibody responses were measured in serum samples. Positive responses in both assays were more common in peripheral blood mononuclear cells from new-onset type 1 diabetic patients compared with control subjects. The proliferative, immunoblot, and autoantibody assays had sensitivities of 58, 91, and 78% with specificities of 94, 83, and 85%, respectively. When cellular assays were combined with autoantibody measurements, the sensitivity of the measurements was 75% with 100% specificity. We conclude that cellular assays performed on peripheral blood have a high degree of accuracy in discriminating responses in subjects with type 1 diabetes from healthy control subjects. They may be useful for assessment of cellular autoimmune responses involved in type 1 diabetes.

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