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Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood
- Source :
- The Journal of Clinical Endocrinology & Metabolism. 104:4521-4530
- Publication Year :
- 2019
- Publisher :
- The Endocrine Society, 2019.
-
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.
- Subjects :
- Male
GENETIC SUSCEPTIBILITY
Insulin Antibodies
Endocrinology, Diabetes and Metabolism
Clinical Biochemistry
CHILDREN
Autoimmunity
Kaplan-Meier Estimate
medicine.disease_cause
Biochemistry
APPEARANCE
Cohort Studies
0302 clinical medicine
Endocrinology
Longitudinal Studies
Child
RISK
0303 health sciences
geography.geographical_feature_category
Glutamate Decarboxylase
Age Factors
Islet
INSULIN
3. Good health
POSITIVITY
Seroconversion
Child, Preschool
Disease Progression
Female
medicine.medical_specialty
Adolescent
Genotype
RELATIVES
PHENOTYPES
030209 endocrinology & metabolism
Context (language use)
Human leukocyte antigen
03 medical and health sciences
HLA-DQ Antigens
Internal medicine
Diabetes mellitus
medicine
Humans
Genetic Predisposition to Disease
TYPE-1
Autoantibodies
Proportional Hazards Models
030304 developmental biology
geography
Type 1 diabetes
business.industry
Biochemistry (medical)
Autoantibody
Infant
HLA-DR Antigens
ALLELES
medicine.disease
Diabetes Mellitus, Type 1
3121 General medicine, internal medicine and other clinical medicine
Immunology
3111 Biomedicine
business
Subjects
Details
- ISSN :
- 19457197 and 0021972X
- Volume :
- 104
- Database :
- OpenAIRE
- Journal :
- The Journal of Clinical Endocrinology & Metabolism
- Accession number :
- edsair.doi.dedup.....286b5523a64545c8fa9f27bcc9a18371