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Autoantibodies against ATP4A are a feature of the abundant autoimmunity that develops in first-degree relatives of patients with type 1 diabetes.
Pediatr. Diabetes 23, 714-720 (2022)
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% CO, 1.3 - 2.8; P = .0004), relatives with the HLA DR4-DQ8/DR4-DQ8 genotype (HR, 3.4; 95% CI, 1.9 - 5.9; P < .0001) and in participants who also had thyroid peroxidase autoantibodies (HR, 3.7; 95% CI, 2.5-5.5; P < .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 < .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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
H+/k+ Atpase ; Autoimmunity ; Parietal Cell Autoantibodies ; Type 1 Diabetes
ISSN (print) / ISBN
1399-543X
e-ISSN
1399-5448
Journal
Pediatric Diabetes
Quellenangaben
Volume: 23,
Issue: 6,
Pages: 714-720
Publisher
Wiley
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Institute for Pancreatic Beta Cell Research (IPI)
Institute of Diabetes Research Type 1 (IDF)
Institute of Diabetes Research Type 1 (IDF)
Grants
German Federal Ministry of Education andResearch to the German Center for DiabetesResearch