ATPase4A Autoreactivity and Its Association With Autoimmune Phenotypes in the Type 1 Diabetes Genetics Consortium Study
| Autor: | Pamela R. Fain, Janet M. Wenzlau, John C. Hutton, Lisa M. Frisch, Thomas J. Gardner, Bruno Annibale |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Male
Endocrinology Diabetes and Metabolism medicine.disease_cause Autoimmunity H(+)-K(+)-Exchanging ATPase 0302 clinical medicine Gene Frequency Prevalence CTLA-4 Antigen Child HLA-DP beta-Chains pernicious anemia Genetics 0303 health sciences biology Middle Aged 3. Good health Child Preschool Female Adult medicine.medical_specialty Adolescent 030209 endocrinology & metabolism PTPN22 03 medical and health sciences Young Adult Parietal Cells Gastric Thyroid peroxidase Internal medicine Internal Medicine medicine Humans Genetic Predisposition to Disease Allele Allele frequency Genetic Association Studies 030304 developmental biology Aged Autoantibodies Advanced and Specialized Nursing Type 1 diabetes business.industry Autoantibody Infant Protein Tyrosine Phosphatase Non-Receptor Type 22 Type 1 Diabetes Genetics Consortium (T1DGC) Autoantibody Workshop medicine.disease Endocrinology Diabetes Mellitus Type 1 Immunology biology.protein business HLA-DRB1 Chains |
| Zdroj: | Diabetes Care |
| ISSN: | 1935-5548 0149-5992 |
| Popis: | Autoantibodies targeting the H+/K+-ATPase proton pump of the gastric parietal cell (parietal cell antibodies [PCA]) are diagnostic of atrophic body gastritis (ABG) leading to pernicious anemia (PA). PCA, ABG, and PA occur in increased frequency in patients with type 1 diabetes and their relatives and are considered “minor” components of forms of autoimmune polyglandular syndrome (APS). A customized radioimmunoprecipitation assay was applied to 6,749 samples from the Type 1 Diabetes Genetics Consortium to measure ATP4A autoreactivity. Autoantibody prevalence was correlated with variants in HLA class II, PTPN22, and CTLA4 genes. With an ATP4A radioimmunoprecipitation assay, PCA were detected in sera from 20.9% of affected individuals. PCA prevalence increased with age and was greater in females (25.3%) than males (16.5%) and among Hispanics (36.3%) and blacks (26.2%) compared with non-Hispanic whites (20.8%) and Asians (16.7%). PCA and other organ-specific autoantibodies GAD65, IA-2, thyroid peroxidase (TPO), 21-hydroxylase (21-OH), and transglutaminase (TG) clustered within families with heritability estimates from 71 to 95%. PCA clustered with TPO, 21-OH, and persistent GAD65 autoantibodies but not with celiac (TG) or IA-2 autoantibodies. PCA-positive subjects showed an increased frequency of DRB1*0404, DPB1*0201, and PTPN22 R620W (rs2476601-T) and a decreased frequency of DRB1*0101, DPB1*0301, and CTLA4 CT60 (rs3087243-T). Genetic variants accounted for 4–5% of the heritable risk for PCA. The same alleles were associated with other autoantibody phenotypes in a consistent pattern. Whereas most of the heritable risk for PCA and other antibodies reflects genetic effects that are tissue specific, parietal cell autoimmunity is a major pathogenetic contributor in APS2. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|