Autoimmune Diabetes From Childhood to Adulthood: The Role of Pancreatic Autoantibodies and HLA-DRB1 Genotype

自身抗体 医学 内科学 1型糖尿病 四分位间距 糖尿病 自身免疫 内分泌学 优势比 背景(考古学) 人类白细胞抗原 胃肠病学 免疫学 抗体 抗原 疾病 生物 古生物学
作者
Inés Urrutia,Rosa Martı́nez,Begona Calvo,Laura Saso-Jiménez,Pedro Lorenzo,Elsa Fernández-Rubio,Alicia Martín-Nieto,Aníbal Aguayo,Itxaso Rica,Sonia Gaztambide,Luís Castaño
出处
期刊:The Journal of Clinical Endocrinology and Metabolism [Oxford University Press]
卷期号:108 (11): e1341-e1346 被引量:3
标识
DOI:10.1210/clinem/dgad277
摘要

Abstract Context Autoimmune diabetes can develop at any age, but unlike early-onset diabetes, adult onset is less well documented. We aimed to compare, over a wide age range, the most reliable predictive biomarkers for this pathology: pancreatic-autoantibodies and HLA-DRB1 genotype. Methods A retrospective study of 802 patients with diabetes (aged 11 months to 66 years) was conducted. Pancreatic autoantibodies at diagnosis: insulin autoantibodies (IAA), glutamate decarboxylase autoantibodies (GADA), islet tyrosine phosphatase 2 autoantibodies (IA2A), and zinc transporter-8 autoantibodies (ZnT8A) and HLA-DRB1 genotype were analyzed. Results Compared with early-onset patients, adults had a lower frequency of multiple autoantibodies, with GADA being the most common. At early onset, IAA was the most frequent in those younger than 6 years and correlated inversely with age; GADA and ZnT8A correlated directly and IA2A remained stable. The absence of HLA-DRB1 risk genotype was associated with higher age at diabetes onset (27.5 years; interquartile range [IQR], 14.3-35.7), whereas the high-risk HLA-DR3/DR4 was significantly more common at lower age (11.9 years; IQR, 7.1-21.6). ZnT8A was associated with DR4/non-DR3 (odds ratio [OR], 1.91; 95% CI, 1.15-3.17), GADA with DR3/non-DR4 (OR, 2.97; 95% CI, 1.55-5.71), and IA2A with DR4/non-DR3 and DR3/DR4 (OR, 3.89; 95% CI, 2.28-6.64, and OR, 3.08; 95% CI, 1.83-5.18, respectively). No association of IAA with HLA-DRB1 was found. Conclusion Autoimmunity and HLA-DRB1 genotype are age-dependent biomarkers. Adult-onset autoimmune diabetes is associated with lower genetic risk and lower immune response to pancreatic islet cells compared with early-onset diabetes.
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