Validity and reproducibility of measurement of islet autoreactivity by T-cell assays in subjects with early type 1 diabetes.
Diabetes
; 58(11): 2588-95, 2009 Nov.
Article
em En
| MEDLINE
| ID: mdl-19675135
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 ANDMETHODS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Reprodutibilidade dos Testes
/
Ilhotas Pancreáticas
/
Diabetes Mellitus Tipo 1
Tipo de estudo:
Clinical_trials
Limite:
Adolescent
/
Adult
/
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos