Table_1_GAD65 Antibody Epitopes and Genetic Background in Latent Autoimmune Diabetes in Youth (LADY).docx

Epitope-specific GAD65Abs and HLA-DR-DQ gene assays help improve the value of risk stratification in autoimmune diabetes mellitus and protect islet function. Identification and early intervention are important for latent autoimmune diabetes in youth (LADY). The aims of this study were to investigate 1) the frequencies of the epitope-specific GAD65Abs and HLA-DR-DQ genes in LADY and 2) the association between HLA-DR-DQ genes and epitope-specific GAD65Abs. Higher frequencies of GAD65-CAb and multiepitope GAD65Abs were observed in young type 1 diabetes, LADY, and old type 1 diabetes subjects than those in latent autoimmune diabetes in adult (LADA) patients. The frequencies of the specific susceptible HLA haplotype DR3, total susceptible HLA haplotypes, and high-risk genotypes were higher in type 1 diabetes and LADY patients than those in LADA patients. In contrast, type 1 diabetes and LADY patients had lower frequencies of low/no genetic risk genotypes (DRX/X) than those of LADA patients. Logistic regression analysis suggested that the susceptible HLA haplotypes were risk factors for glutamic acid decarboxylase antibody (GADA) multiepitope positivity in autoimmune diabetes mellitus. LADY may be more severe than LADA, and LADY seemed to be a transitional type of type 1 diabetes and LADA. GADA epitope and HLA-DR-DQ gene assays are important for risk stratification in autoimmune diabetes mellitus and protection of islet function.

特异性表位GAD65Abs及HLA-DR-DQ基因检测有助于提升自身免疫性糖尿病的疾病风险分层价值，并保护胰岛功能。对于青少年潜在自身免疫性糖尿病（LADY）的识别和早期干预至关重要。本研究旨在探讨1）LADY中特异性表位GAD65Abs和HLA-DR-DQ基因的频率，以及2）HLA-DR-DQ基因与特异性GAD65Abs之间的关联。在年轻1型糖尿病、LADY和老年1型糖尿病受试者中观察到GAD65-CAb和多表位GAD65Abs的频率高于潜在自身免疫性糖尿病成人（LADA）患者。在1型糖尿病和LADY患者中，特异性易感HLA单倍型DR3、总易感HLA单倍型和高风险基因型频率高于LADA患者。相反，1型糖尿病和LADY患者中低/无遗传风险基因型（DRX/X）的频率低于LADA患者。逻辑回归分析表明，易感HLA单倍型是自身免疫性糖尿病中谷氨酸脱羧酶抗体（GADA）多表位阳性的风险因素。LADY可能比LADA更为严重，且LADY似乎是一种介于1型糖尿病和LADA之间的过渡型。GADA表位和HLA-DR-DQ基因检测对于自身免疫性糖尿病的风险分层和胰岛功能的保护具有重要意义。