Dynamics of Islet Autoantibodies During Prospective Follow-Up From Birth to Age 15 Years

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Pöllänen , P M , Ryhänen , S J , Toppari , J , Ilonen , J , Vähäsalo , P , Veijola , R , Siljander , H & Knip , M 2020 , ' Dynamics of Islet Autoantibodies During Prospective Follow-Up From Birth to Age 15 Years ' , Journal of Clinical Endocrinology and Metabolism , vol. 105 , no. 12 , 624 . https://doi.org/10.1210/clinem/dgaa624

Title: Dynamics of Islet Autoantibodies During Prospective Follow-Up From Birth to Age 15 Years
Author: Pöllänen, Petra M.; Ryhänen, Samppa J.; Toppari, Jorma; Ilonen, Jorma; Vähäsalo, Paula; Veijola, Riitta; Siljander, Heli; Knip, Mikael
Contributor organization: HUS Children and Adolescents
Faculty of Medicine
Children's Hospital
University of Helsinki
Helsinki University Hospital Area
CAMM - Research Program for Clinical and Molecular Metabolism
Research Programs Unit
Lastentautien yksikkö
Date: 2020-12
Language: eng
Number of pages: 14
Belongs to series: Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
DOI: https://doi.org/10.1210/clinem/dgaa624
URI: http://hdl.handle.net/10138/324073
Abstract: Context: We set out to characterize the dynamics of islet autoantibodies over the first 15 years of life in children carrying genetic susceptibility to type 1 diabetes (T1D). We also assessed systematically the role of zinc transporter 8 autoantibodies (ZnT8A) in this context. Design: HLA-predisposed children (N = 1006, 53.0% boys) recruited from the general population during 1994 to 1997 were observed from birth over a median time of 14.9 years (range, 1.9-15.5 years) for ZnT8A, islet cell (ICA), insulin (IAA), glutamate decarboxylase (GADA), and islet antigen-2 (IA-2A) antibodies, and for T1D. Results: By age 15.5 years, 35 (3.5%) children had progressed to T1D. Islet autoimmunity developed in 275 (27.3%) children at a median age of 7.4 years (range, 0.3-15.1 years). The ICA seroconversion rate increased toward puberty, but the biochemically defined autoantibodies peaked at a young age. Before age 2 years, ZnT8A and IAA appeared commonly as the first autoantibody, but in the preschool years IA-2A- and especially GADA-initiated autoimmunity increased. Thereafter, GADA-positive seroconversions continued to appear steadily until ages 10 to 15 years. Inverse IAA seroconversions occurred frequently (49.3% turned negative) and marked a prolonged delay from seroconversion to diagnosis compared to persistent IAA (8.2 vs 3.4 years; P = .01). Conclusions: In HLA-predisposed children, the primary autoantibody is characteristic of age and might reflect the events driving the disease process toward clinical T1D. Autoantibody persistence affects the risk of T1D. These findings provide a framework for identifying disease subpopulations and for personalizing the efforts to predict and prevent T1D.
Subject: type 1 diabetes
islet autoantibodies
3121 General medicine, internal medicine and other clinical medicine
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: acceptedVersion

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