title: Analysis of T-cell assays to measure autoimmune responses in subjects with type 1 diabetes: results of a blinded controlled study.
abstract: 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.
authors.affiliation: Immune Teolerance Network, Bethesda, Maryland, USA.
authors.forename: Vicki
authors.initials: V
authors.lastname: Seyfert-Margolis
authors.forename: Trang D
authors.initials: TD
authors.lastname: Gisler
authors.forename: Adam L
authors.initials: AL
authors.lastname: Asare
authors.forename: Richard S
authors.initials: RS
authors.lastname: Wang
authors.forename: H Michael
authors.initials: HM
authors.lastname: Dosch
authors.forename: Barbara
authors.initials: B
authors.lastname: Brooks-Worrell
authors.forename: George S
authors.initials: GS
authors.lastname: Eisenbarth
authors.forename: Jerry P
authors.initials: JP
authors.lastname: Palmer
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Gitelman
authors.forename: Gerald T
authors.initials: GT
authors.lastname: Nepom
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: Kevan C
authors.initials: KC
authors.lastname: Herold
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000032:analysis; D015551:Autoimmunity / Q000276:immunology*; D049109:Cell Proliferation; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000032:analysis; D006801:Humans; D015151:Immunoblotting; D007527:Isoenzymes / Q000032:analysis; D008297:Male; D012680:Sensitivity and Specificity; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001323:Autoantibodies; C096322:ICA512 autoantibody; D007527:Isoenzymes; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2