Autoantibodies against ATP4A are a feature of the abundant autoimmunity that develops in first-degree relatives of patients with type 1 diabetes.

Zielmann, Marie-Luise; Jolink, Manja; Winkler, Christiane; Eugster, Anne; Müller, Denise; Scholz, Marlon; Ziegler, Anette-G; Bonifacio, Ezio

doi:10.1111/pedi.13361

journal article

Document type:: Article; Journal Article; Research Support, Non-U.S. Gov't
Author(s):: Zielmann, Marie-Luise; Jolink, Manja; Winkler, Christiane; Eugster, Anne; Müller, Denise; Scholz, Marlon; Ziegler, Anette-G; Bonifacio, Ezio
Title:: Autoantibodies against ATP4A are a feature of the abundant autoimmunity that develops in first-degree relatives of patients with type 1 diabetes.
Abstract:: OBJECTIVE: Type 1 diabetes is associated with autoantibodies to different organs that include the gut. The objective of the study was to determine the risk of developing gastric parietal cell autoimmunity in relation to other autoimmunity in individuals with a family history of type 1 diabetes. METHODS: Autoantibodies to the parietal cell autoantigen, H+ /K+ ATPase subunit A (ATP4A) was measured in 2218 first-degree relatives of patients with type 1 diabetes, who were prospectively followed from birth for a median of 14.5 years. All were also tested regularly for the development of islet autoantibodies, transglutaminase autoantibodies, and thyroid peroxidase autoantibodies. RESULTS: The cumulative risk to develop ATP4A autoantibodies was 8.1% (95% CI, 6.6-9.6) by age 20 years with a maximum incidence observed at age 2 years. Risk was increased in females (HR, 1.9; 95% CI, 1.3-2.8; p = 0.0004), relatives with the HLA DR4-DQ8/DR4-DQ8 genotype (HR, 3.4; 95% CI, 1.9-5.9; p < 0.0001) and in participants who also had thyroid peroxidase autoantibodies (HR, 3.7; 95% CI, 2.5-5.5; p < 0.0001). Risk for at least one of ATP4A-, islet-, transglutaminase-, or thyroid peroxidase-autoantibodies was 24.7% (95% CI, 22.6-26.7) by age 20 years and was 47.3% (95% CI, 41.3-53.3) in relatives who had an HLA DR3/DR4-DQ8, DR4-DQ8/DR4-DQ8, or DR3/DR3 genotype (p < 0.0001 vs. other genotypes). CONCLUSIONS: Relatives of patients with type 1 diabetes who have risk genotypes are at very high risk for the development of autoimmunity against gastric and other organs.
Journal title abbreviation:: Pediatr Diabetes
Year:: 2022
Journal volume:: 23
Journal issue:: 6
Pages contribution:: 714-720
Fulltext / DOI:: doi:10.1111/pedi.13361
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/35561070
Print-ISSN:: 1399-543X
TUM Institution:: Klinik und Poliklinik für Kinder- und Jugendmedizin
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Klinik und Poliklinik für Kinder- und Jugendmedizin (Prof. Hauer)2022