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Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood.
J Clin Endocrinol Metab. 2019 10 01; 104(10):4521-4530.JC

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.

Authors+Show Affiliations

Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland.Department of Paediatrics, PEDEGO Research Unit, Medical Research Center, University of Oulu, Oulu, Finland. Department of Children and Adolescents, Oulu University Hospital, Oulu, Finland.Department of Paediatrics, University of Turku and Turku University Hospital, Turku, Finland. Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland. Clinical Microbiology, Turku University Hospital, Turku, Finland.Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland.Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.Department of Paediatrics, University of Turku and Turku University Hospital, Turku, Finland. Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland.Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland. Folkhälsan Research Center, Helsinki, Finland. Tampere Center for Child Health Research, Tampere University Hospital, Tampere, Finland.Clinical Research Centre, Medical University of Bialystok, Bialystok, Poland. Szentágothai Research Centre, University of Pécs, Pécs, Hungary.Immunogenetics Laboratory, Institute of Biomedicine, University of Turku, Turku, Finland. Clinical Microbiology, Turku University Hospital, Turku, Finland.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

31120497

Citation

Bauer, Witold, et al. "Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood." The Journal of Clinical Endocrinology and Metabolism, vol. 104, no. 10, 2019, pp. 4521-4530.
Bauer W, Veijola R, Lempainen J, et al. Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood. J Clin Endocrinol Metab. 2019;104(10):4521-4530.
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. The Journal of Clinical Endocrinology and Metabolism, 104(10), 4521-4530. https://doi.org/10.1210/jc.2019-00421
Bauer W, et al. Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood. J Clin Endocrinol Metab. 2019 10 1;104(10):4521-4530. PubMed PMID: 31120497.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Age at Seroconversion, HLA Genotype, and Specificity of Autoantibodies in Progression of Islet Autoimmunity in Childhood. AU - Bauer,Witold, AU - Veijola,Riitta, AU - Lempainen,Johanna, AU - Kiviniemi,Minna, AU - Härkönen,Taina, AU - Toppari,Jorma, AU - Knip,Mikael, AU - Gyenesei,Attila, AU - Ilonen,Jorma, PY - 2019/02/21/received PY - 2019/05/17/accepted PY - 2019/5/24/pubmed PY - 2020/6/9/medline PY - 2019/5/24/entrez SP - 4521 EP - 4530 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 104 IS - 10 N2 - 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. SN - 1945-7197 UR - https://www.unboundmedicine.com/medline/citation/31120497/Age_at_Seroconversion_HLA_Genotype_and_Specificity_of_Autoantibodies_in_Progression_of_Islet_Autoimmunity_in_Childhood_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2019-00421 DB - PRIME DP - Unbound Medicine ER -