Hierarchical order of autoantigen spreading and progression to T1D in the TEDDY Study

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Abstract Summary

Background: The first appearing diabetes-associated autoantibody (Ab) has been shown to vary risk of T1D. Here, we assessed risk of autoantigen spreading by appearance of the second-appearing Ab and further progression to T1D in the Environmental Determinants of Diabetes in the Young (TEDDY) study.

Methods: HLA-eligible children were followed for development of primary Abs (GADA, IA-2A and IAA) and progression to T1D. Primary persistent Ab was defined as positive for a specific Ab at two consecutive visits confirmed by two laboratories.  ZnT8A was measured on all children who developed a primary Ab.

Results: There were 633 children who developed a persistent first-appearing Ab (IAA n=260, GADA n=296, or combination of GADA and IAA n=77) with a median of 9 years follow up from birth. GADA or IAA were also more likely to appear as a second appearing Ab. There was no significant difference in the antigen-specific risk of either ZnT8A or IA-2A appearing as a second Ab.In children with IAA as the first appearing, IA-2A (HR 7.7, 95%CI 4-15, p<0.0001) and GADA (HR 2.3, 95%CI 1.2-4.2, p=0.009) as a second-appearing Ab conferred increased risk of progression to T1D as compared with not developing a second Ab; while, ZnT8A did not contribute to risk of progression to T1D (HR 1.4, 95%CI 0.6-3.4, p=0.4).In children who developed GADA as first-appearing, appearance of IA-2A (HR 10.4, 95%CI 4-26, p<0.0001), IAA (HR 5.5, 95%CI 2.3-13.0, p<0.0001) and ZnT8A (HR 2.98, 95%CI 1-8, p=0.03) as a second Ab conferred an increased risk of progression to T1D. Among those with both IAA and GADA, IA-2A as the second Ab conferred a higher risk of progression to T1D compared with ZnT8A (HR 2.4, 95%CI 1.0-5.6, p=0.05).

Conclusion: The hierarchical order of autoantigen spreading augments estimation of the risk of progression to clinical onset of T1D.

Submission ID :
IDS11199
Submission Type
Abstract Topics
Health Informatics Institute, University of South Florida
University of South Florida, USA
Institute of Diabetes Research, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich-Neuherberg, Germany
National Institute of Diabetes and Digestive and Kidney Diseases
University of Turku
Pacific Northwest Diabetes Research Institute, USA
University of Bristol
Barbara Davis Center
Barbara Davis Center
Diabetes Center of Excellence, University of Florida
CRTD Center for Regenerative Therapies Dresden
Lund University, Lund (Sweden)

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KEY DATES

Event dates:
Thursday 25 October - Monday 29 October 2018

Abstract submission deadline:
Monday 14 May 2018

Abstract notification:
July 2018

Early registration deadline:
Monday 3 September 2018

Registration deadline:
Monday 15 October 2018

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