Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2013 Oct;13(5):608-15.
doi: 10.1007/s11892-013-0405-9.

Novel diabetes autoantibodies and prediction of type 1 diabetes

Janet M Wenzlau  1 , John C Hutton
Affiliations
Review

Novel diabetes autoantibodies and prediction of type 1 diabetes

Janet M Wenzlau et al. Curr Diab Rep. 2013 Oct.

Abstract

Autoantibodies are currently the most robust biomarkers of type 1 diabetes and are frequently used to establish entry criteria for the participation of genetically at-risk individuals in secondary prevention/intervention clinical trials. Since their original description almost 40 years ago, considerable efforts have been devoted toward identifying the precise molecular targets that are recognized. Such information can have significant benefit for developing improved metrics for identifying/stratifying of at-risk subjects, developing potential therapeutic targets, and advancing understanding of the pathophysiology of the disease. Currently, four major molecular targets ([pro]insulin, GAD65, IA-2, and ZnT8) have been confirmed, with approximately 94% of all subjects with a clinical diagnosis of type 1 diabetes expressing autoantibodies to at least one of these molecules at clinical onset. In this review, we summarize some of the salient properties of these targets that might contribute to their autoantigenicity and methods that have been used in attempts to identify new components of the humoral autoresponse.

PubMed Disclaimer

Conflict of interest statement

Compliance with Ethics Guidelines: Conflict of Interest Janet M. Wenzlau receives royalties from Kronus for ZnT8 patent #CU1673H

John C. Hutton received royalties from Kronus for ZnT8 patent #CU1673H

Figures

Fig. 1
Fig. 1
Combining ZnT8A with IAA, GADA, and IA2A assays increases the sensitivity of autoimmune detection. Sera obtained from recently diabetic subjects ranging in age from 2 to 40 years were assayed in parallel with RIAs to insulin (INS), GAD65 (GAD), IA-2, and ZnT8. Overall prevalence is shown for each antigen, although it should be noted that this can vary significantly with age of onset, especially for IAA. In this cohort, the combined measurement of GADA, IAA, and IA2A detected autoimmunity in ∼86% of subjects. Inclusion of ZnT8A increased this to ∼96%, and ∼25% reduction in the number of autoantibody negative individuals
Fig. 2
Fig. 2
Homo-dimeric ZnT8 antigen probes enhance sensitivity. Sera from newly diabetic subjects were assayed in parallel with monomeric and homo-dimeric ZnT8 variant probes. Detected prevalences with monomers versus dimers were X v Y, X1 v Y1, and X2 v Y2 for the R, W, and Q probe pairs, respectively. Red lines indicate cutoff values
See this image and copyright information in PMC

References

    1. Rosmalen JG, van Ewijk W, Leenen PJ. T-cell education in autoimmune diabetes: teachers and students. Trends Immunol. 2002;23(1):40–6. - PubMed
    1. Pihoker C, Gilliam l, Hampe C, Lernmark A. Autoantibodies in diabetes. Diabetes. 2005;54:S52–61. - PubMed
    1. Eisenbarth GS. Type I diabetes mellitus. A chronic autoimmune disease. N Engl J Med. 1986;314(21):1360–8. - PubMed
    1. Oling V, Marttila J, Ilonen J, Kwok WW, Nepom G, Knip M, et al. GAD65- and proinsulin-specific CD4+ T-cells detected by MHC class II tetramers in peripheral blood of type 1 diabetes patients and at-risk subjects. J Autoimmun. 2005;25(3):235–43. - PubMed
    1. Kelemen K, Gottlieb PA, Putnam AL, Davidson HW, Wegmann DR, Hutton JC. HLA-DQ8-associated T cell responses to the diabetes autoantigen phogrin (IA-2 beta) in human prediabetes. J Immunol. 2004;172(6):3955–62. - PubMed

Publication types

MeSH terms