A clinical research consortium sponsored by NIAID and JDRF

Type 1 Diabetes Autoantibody Core

Principal Investigator:
George Eisenbarth, University of Colorado, Aurora, CO
Study Code: 
Core:T1DAA

Abstract

The ITN Autoantibody Core analyzes patient serum for the presence of autoantibodies using semi-automated high throughput radioassays.

Translated cDNA constructs are used to express autoantigens for the assay. Currently, there are three anti-islet autoantibody tests (GAD65, ICA512 and mIAAA), one Addison's disease related autoantibody test (21-
hdryoxlyase) and one Celiac disease-related autoantibody test (tissue transglutaminase). New assays are in development. All of these assays can be run with Ig isotyping (IgG subclasses, IgA, IgE, and IgM).

This core has participated in the 2007 CDC-sponsored Diabetes Autoantibody Standardization Program (DASP), comparing multiple national/international laboratories' measures of GAD65, IA-2 (ICA512) and insulin autoantibodies. This laboratory had one of the highest reported sensitivity and specificities in an analysis of 100 controls and 50 patients with new onset diabetes. The sensitivity and specificity are 90% and 96% for GAD65, 64% and 98% for ICA512bdc, 68% and 99% for IA-2ic, 66% and 99% for mIAA, and 58% and 99% for ZnT8. 

Manuscripts

Yu L, Wang J, O'Dell JR, Oates J, Arend WP, Eisenbarth GS. Anti-dsDNA antibody assay: high specificity and sensitivity with a filtration radioassay in comparison to low specificity with the standard ELISA. J Rheumatol 34:734-739, 2007. [PubMed] [Reprint]
Miao D, Yu L, Eisenbarth GS. Role of autoantibodies in type 1 diabetes. Front Biosci 12:1889-1898, 2007 [PubMed] [Reprint]
Yu J, Steck AK, Babu S, Yu L, Miao D, McFann K, Hutton J, Eisenbarth GS, Klingensmith G. Single nucleotide transcription factor 7-like 2 (TCF7L2) gene polymorphisms in antiislet autoantibody-negative patients at onset of diabetes. J Clin Endocrinol Metab 94:504-10, 2009 [PubMed] [Reprint]
Baschal EE, Aly TA, Babu SR, Fernando MS, Yu L, Miao D et al. HLA-DPB1*0402 protects against type 1A diabetes autoimmunity in the highest risk DR3-DQB1*0201/DR4-DQB1*0302 DAISY population. Diabetes 56:2405-2409, 2007. [PubMed] [Reprint]
Zhang L, Barker JM, Babu S, Su M, Stenerson M, Cheng M et al. A robust immunoassay for anti-interferon autoantibodies that is highly specific for patients with autoimmune polyglandular syndrome type 1. Clin Immunol 125:131-137, 2007. [PubMed] [Reprint]
Wang J, Miao D, Babu S, Yu J, Barker J, Klingensmith G, Rewers M, Eisenbarth GS, and Yu L. Prevalence of autoantibody-negative diabetes is not rare at all ages and increases with older age and obesity. J Clin Endocrinol Metab 92:88-92, 2007. [PubMed] [Reprint]
Babaya N, Liu E, Miao D, Li M, Yu L, Eisenbarth GS. Murine high specificity/sensitivity competitive europium insulin autoantibody assay. Diabetes Technol Ther 11:227-33, 2009. [PubMed] [Reprint]
Liu E, Eisenbarth GS. Accepting clocks that tell time poorly: fluid-phase versus standard ELISA autoantibody assays. Clin Immunol 125:120-126, 2007. [PubMed] [Reprint]

Meeting Abstracts

Eisenbarthh GS. Autoantibodies in type 1 diabetes and neurological disorders. XXIIth International Congress of Immunology, Montreal, Canada, July 18-23, 2004. [Abstract]