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Diabetes. 2009 Nov;58(11):2588-95. doi: 10.2337/db09-0249. Epub 2009 Aug 12.

Validity and reproducibility of measurement of islet autoreactivity by T-cell assays in subjects with early type 1 diabetes.

Author information

  • 1Yale University, New Haven, Connecticut, USA. kevan.herold@yale.edu

Abstract

OBJECTIVE:

Type 1 diabetes results from an immunemediated destruction of beta-cells, likely to be mediated by T lymphocytes, but the sensitivity, specificity, and other measures of validity of existing assays for islet autoreactive T-cells are not well established. Such assays are vital for monitoring responses to interventions that may modulate disease progression.

RESEARCH DESIGN AND METHODS:

We studied the ability of cellular assays to discriminate responses in patients with type 1 diabetes and normal control subjects in a randomized blinded study in the U.S. and U.K. We evaluated the reproducibility of these measurements overall and to individual analytes from repeat collections.

RESULTS:

Responses in the cellular immunoblot, U.K.-ELISPOT, and T-cell proliferation assays could differentiate patients from control subjects with odds ratios of 21.7, 3.44, and 3.36, respectively, with sensitivity and specificity as high as 74 and 88%. The class II tetramer and U.S. ELISPOT assays performed less well. Despite the significant association of the responses with type 1 diabetes, the reproducibility of the measured responses, both overall and individual analytes, was relatively low. Positive samples from normal control subjects (i.e., false positives) were generally isolated to single assays.

CONCLUSIONS:

The cellular immunoblot, U.K.-ELISPOT, and T-cell proliferation assays can distinguish responses from patients with type 1 diabetes and healthy control subjects. The limited reproducibility of the measurements overall and of responses to individual analytes may reflect the difficulty in detection of low frequency of antigen-specific T-cells or variability in their appearance in peripheral blood.

PMID:
19675135
[PubMed - indexed for MEDLINE]
PMCID:
PMC2768166
Free PMC Article
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