Time-Resolved Autoantibody Profiling Facilitates Stratification of Preclinical Type 1 Diabetes in Children.

Abstract

Progression to clinical type 1 diabetes varies among children who develop β-cell autoantibodies. Differences in autoantibody patterns could relate to disease progression and etiology. Here we modeled complex longitudinal autoantibody profiles by using a novel wavelet-based algorithm. We identified clusters of similar profiles associated with various types of progression among 600 children from The Environmental Determinants of Diabetes in the Young (TEDDY) birth cohort study; these children developed persistent insulin autoantibodies (IAA), GAD autoantibodies (GADA), insulinoma-associated antigen 2 autoantibodies (IA-2A), or a combination of these, and they were followed up prospectively at 3- to 6-month intervals (median follow-up 6.5 years). Children who developed multiple autoantibody types (n = 370) were clustered, and progression from seroconversion to clinical diabetes within 5 years ranged between clusters from 6% (95% CI 0, 17.4) to 84% (59.2, 93.6). Children who seroconverted early in life (median age <2 years) and developed IAA and IA-2A that were stable-positive on follow-up had the highest risk of diabetes, and this risk was unaffected by GADA status. Clusters of children who lacked stable-positive GADA responses contained more boys and lower frequencies of the HLA-DR3 allele. Our novel algorithm allows refined grouping of β-cell autoantibody-positive children who distinctly progressed to clinical type 1 diabetes, and it provides new opportunities in searching for etiological factors and elucidating complex disease mechanisms.

• Authors: David Endesfelder, Wolfgang Zu Castell, Ezio Bonifacio, Marian Rewers, William A Hagopian, Jin-Xiong She, Åke Lernmark, Jorma Toppari, Kendra Vehik, Alistair J K Williams, Liping Yu, Beena Akolkar, Jeffrey P Krischer, Anette-G Ziegler, Peter Achenbach, TEDDY Study Group
• Journal: Diabetes (Diabetes) Vol. 68 Issue 1 Pg. 119-130 (01 2019) ISSN: 1939-327X [Electronic] United States
• PMID: 30305370 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, P.H.S.)
• Copyright: © 2018 by the American Diabetes Association.

Chemical References

• Autoantibodies
• ICA512 autoantibody
• Insulin Antibodies

Topics

• Adolescent
• Algorithms
• Autoantibodies (metabolism)
• Child
• Child, Preschool
• Diabetes Mellitus, Type 1 (immunology, metabolism)
• Female
• Humans
• Infant
• Insulin Antibodies (metabolism)
• Kaplan-Meier Estimate
• Male
• Prospective Studies