Extrapancreatic autoantibody profiles in type I diabetes.
Extrapancreatic autoantibody profiles in type I diabetes.
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DOI：
10.1371/journal.pone.0045216
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Iadarola MJ
中科院分区：
文献类型：
--
作者：
Burbelo PD;Lebovitz EE;Bren KE;Bayat A;Paviol S;Wenzlau JM;Barriga KJ;Rewers M;Harlan DM;Iadarola MJ
I 型糖尿病 (T1D) 是一种自身免疫性疾病，其特征是胰腺中产生胰岛素的 β 细胞遭到破坏。尽管已知几种胰岛细胞自身抗原，但自身抗体靶标的广度和谱尚未得到充分探索。这里使用荧光素酶免疫沉淀系统 (LIPS) 抗体分析技术来并行研究胰岛和其他器官特异性自身抗体反应。对 93 名对照者和 50 名 T1D 受试者的初始队列的检查显示，16% 的糖尿病受试者表现出抗胃 ATP 酶自身抗体，该抗体与针对 GAD65、IA2 或 IA2-β 的自身抗体不相关。对具有 18 个潜在自身抗体靶标的第二组进行的更详细研究揭示了针对胰岛细胞自身抗原（包括 ZnT8 的两种多态性变体）的自身抗体反应的显着异质性。一部分 T1D 受试者表现出针对多个器官特异性靶标的自身抗体，包括胃 ATP 酶 (11%)、甲状腺过氧化物酶 (14%) 和针对组织转谷氨酰胺酶的抗 IgA 自身抗体 (12%)。尽管一些 T1D 受试者表现出针对肺相关蛋白 KCNRG (6%) 和 S100-β (8%) 的自身抗体，但没有检测到针对几种细胞因子的具有统计学意义的自身抗体。使用热图对整体自身抗体谱进行分析揭示了两个数量大致相似的主要亚组，包括具有和不具有器官特异性自身抗体的 T1D 受试者。在器官特异性亚组中，抗胃 ATP 酶、抗甲状腺过氧化物酶和抗转谷氨酰胺酶血清阳性之间的重叠极小，并且这些自身抗体与胰岛细胞自身抗体不相关。对第三组的检查（包括从高危个体中前瞻性收集的纵向样本）显示，在检测到胰岛自身抗体之前和 T1D 临床发病之前，数个个体中就存在抗胃 ATP 酶自身抗体。总而言之，这些结果表明，源自胰岛和器官特异性靶标的自身抗体肖像可能有助于加强 T1D 的临床管理。
Type I diabetes (T1D) is an autoimmune disease characterized by destruction of insulin-producing β-cells in the pancreas. Although several islet cell autoantigens are known, the breadth and spectrum of autoantibody targets has not been fully explored. Here the luciferase immunoprecipitation systems (LIPS) antibody profiling technology was used to study islet and other organ-specific autoantibody responses in parallel. Examination of an initial cohort of 93 controls and 50 T1D subjects revealed that 16% of the diabetic subjects showed anti-gastric ATPase autoantibodies which did not correlate with autoantibodies against GAD65, IA2, or IA2-β. A more detailed study of a second cohort with 18 potential autoantibody targets revealed marked heterogeneity in autoantibody responses against islet cell autoantigens including two polymorphic variants of ZnT8. A subset of T1D subjects exhibited autoantibodies against several organ-specific targets including gastric ATPase (11%), thyroid peroxidase (14%), and anti-IgA autoantibodies against tissue transglutaminase (12%). Although a few T1D subjects showed autoantibodies against a lung-associated protein KCNRG (6%) and S100-β (8%), no statistically significant autoantibodies were detected against several cytokines. Analysis of the overall autoantibody profiles using a heatmap revealed two major subgroups of approximately similar numbers, consisting of T1D subjects with and without organ-specific autoantibodies. Within the organ-specific subgroup, there was minimal overlap among anti-gastric ATPase, anti-thyroid peroxidase, and anti-transglutaminase seropositivity, and these autoantibodies did not correlate with islet cell autoantibodies. Examination of a third cohort, comprising prospectively collected longitudinal samples from high-risk individuals, revealed that anti-gastric ATPase autoantibodies were present in several individuals prior to detection of islet autoantibodies and before clinical onset of T1D. Taken together, these results suggest that autoantibody portraits derived from islet and organ-specific targets will likely be useful for enhancing the clinical management of T1D.
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影响因子：
7.4
作者：
Burbelo PD;Seam N;Groot S;Ching KH;Han BL;Meduri GU;Iadarola MJ;Suffredini AF
通讯作者：
Suffredini AF
用于自身抗体的新发光测定法对哺乳动物预制作的胰岛素瘤相关蛋白2。
影响因子：
16.2
作者：
Burbelo, Peter D.;Hirai, Hiroki;Leahy, Hannah;Lernmark, Ake;Ivarsson, Sten A.;Iadarola, Michael J.;Notkins, Abner Louis
通讯作者：
Notkins, Abner Louis
影响因子：
16.2
作者：
Burbelo PD;Hirai H;Issa AT;Kingman A;Lernmark A;Ivarsson SA;Notkins AL;Iadarola MJ
通讯作者：
Iadarola MJ
影响因子：
8.2
作者：
Lampasona, V;Bonfanti, R;Bonifacio, E
通讯作者：
Bonifacio, E
影响因子：
7.7
作者：
LANDINOLSSON, M;KARLSSON, FA;OSTMAN, J
通讯作者：
OSTMAN, J