Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, 1120 15th Street, Augusta, GA, 30912, USA.
Department of Internal Medicine, Yale School of Medicine, New Haven, CT, CT06510, USA.
Nat Commun. 2022 Nov 1;13(1):6527. doi: 10.1038/s41467-022-34341-2.
Type 1 diabetes (T1D) is an autoimmune disease, characterized by the presence of autoantibodies to protein and non-protein antigens. Here we report the identification of specific anti-carbohydrate antibodies (ACAs) that are associated with pathogenesis and progression to T1D. We compare circulatory levels of ACAs against 202 glycans in a cross-sectional cohort of T1D patients (n = 278) and healthy controls (n = 298), as well as in a longitudinal cohort (n = 112). We identify 11 clusters of ACAs associated with glycan function class. Clusters enriched for aminoglycosides, blood group A and B antigens, glycolipids, ganglio-series, and O-linked glycans are associated with progression to T1D. ACAs against gentamicin and its related structures, G418 and sisomicin, are also associated with islet autoimmunity. ACAs improve discrimination of T1D status of individuals over a model with only clinical variables and are potential biomarkers for T1D.
1 型糖尿病(T1D)是一种自身免疫性疾病,其特征是存在针对蛋白质和非蛋白质抗原的自身抗体。在这里,我们报告了与 T1D 发病机制和进展相关的特定抗碳水化合物抗体(ACAs)的鉴定。我们在 T1D 患者(n=278)和健康对照者(n=298)的横断面队列中以及在纵向队列(n=112)中比较了针对 202 种聚糖的循环 ACAs 水平。我们确定了与聚糖功能类别相关的 11 个 ACA 簇。富含氨基糖苷类、血型 A 和 B 抗原、糖脂、神经节苷脂和 O-连接聚糖的簇与 T1D 的进展相关。针对庆大霉素及其相关结构、G418 和西索米星的 ACA 也与胰岛自身免疫有关。ACAs 提高了个体 T1D 状态的区分度,优于仅具有临床变量的模型,并且是 T1D 的潜在生物标志物。