Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood

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Bauer , W , Veijola , R , Lempainen , J , Kiviniemi , M , Härkönen , T , Toppari , J , Knip , M , Gyenesei , A & Ilonen , J 2019 , ' Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood ' , Journal of Clinical Endocrinology and Metabolism , vol. 104 , no. 10 , pp. 4521-4530 . https://doi.org/10.1210/jc.2019-00421

Title: Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood
Author: Bauer, Witold; Veijola, Riitta; Lempainen, Johanna; Kiviniemi, Minna; Härkönen, Taina; Toppari, Jorma; Knip, Mikael; Gyenesei, Attila; Ilonen, Jorma
Contributor: University of Helsinki, Diabetes and Obesity Research Program
University of Helsinki, HUS Children and Adolescents
Date: 2019-10
Language: eng
Number of pages: 10
Belongs to series: Journal of Clinical Endocrinology and Metabolism
ISSN: 0021-972X
URI: http://hdl.handle.net/10138/312969
Abstract: Context: Children with initial autoantibodies to either insulin (IAA) or glutamic acid decarboxylase (GADA) differ in peak age of seroconversion and have different type 1 diabetes (T1D) risk gene associations, suggesting heterogeneity in the disease process. Objective: To compare the associations of age at seroconversion, HLA risk, and specificity of secondary autoantibodies with the progression of islet autoimmunity between children with either IAA or GADA as their first autoantibody. Design and methods: A cohort of 15,253 children with HLA-associated increased risk of T1D participated in a follow-up program in which islet autoantibodies were regularly measured. The median follow-up time was 6.7 years. Spearman correlation, Kaplan-Meier survival plots, and Cox proportional-hazard models were used for statistical analyses. Results: Persistent positivity for at least one of the tested autoantibodies was detected in 998 children; 388 of children progressed to clinical T1D. Young age at initial seroconversion was associated with a high probability of expansion of IAA-initiated autoimmunity and progression to clinical diabetes, whereas expansion of GADA-initiated autoimmunity and progression to diabetes were not dependent on initial seroconversion age. The strength of HLA risk affected the progression of both IAA- and GADA-initiated autoimmunity. The simultaneous appearance of two other autoantibodies increased the rate of progression to diabetes compared with that of a single secondary autoantibody among subjects with GADA-initiated autoimmunity but not among those with IAA as the first autoantibody. Conclusions: Findings emphasize the differences in the course of islet autoimmunity initiated by either IAA or GADA supporting heterogeneity in the pathogenic process.
Subject: GENETIC SUSCEPTIBILITY
TYPE-1
RISK
CHILDREN
APPEARANCE
POSITIVITY
PHENOTYPES
RELATIVES
ALLELES
INSULIN
3111 Biomedicine
3121 General medicine, internal medicine and other clinical medicine
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