Autoimmunity against INS-IGF2 Protein Expressed in Human Pancreatic Islets
Autoimmunity against INS-IGF2 Protein Expressed in Human Pancreatic Islets
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DOI：
10.1074/jbc.m113.478222
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发表时间：
2013-10-04
影响因子：
4.8
通讯作者：
Lernmark, Ake
中科院分区：
文献类型：
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作者：
Kanatsuna, Norio;Taneera, Jalal;Lernmark, Ake
胰岛素是胰岛自身免疫和 1 型糖尿病进展中的主要自身抗原。有人提出，胰岛素 B 链可能对 1 型糖尿病的胰岛素自身免疫至关重要。 INS-IGF2 由前胰岛素原信号肽、胰岛素 B 链和 C 肽的 8 个氨基酸以及 IGF2 基因的 138 个氨基酸组成。我们的目的是确定新诊断的 1 型糖尿病儿童和对照组的人胰岛和自身抗体中 INS-IGF2 的表达。 INS-IGF2 主要在 β 细胞中表达，与患有 2 型糖尿病 (p = 0.006) 或高 HbA1c 水平 (p < 0.001) 的供体相比，正常胰岛中的 INS-IGF2 显示出更高的表达水平。与健康对照者 (n = 355；p < 0.001) 相比，新诊断的 1 型糖尿病患者 (n = 304) INS-IGF2 自身抗体水平升高。用冷胰岛素和 INS-IGF2 替代显示，与对照组相比，更多患者具有双反应性胰岛素-INS-IGF2 自身抗体。这些数据表明，含有前胰岛素原信号肽、B 链和 C 肽的 8 个氨基酸的 INS-IGF2 可能是 1 型糖尿病的自身抗原。 INS-IGF2 和胰岛素可能共享自身抗体结合位点，从而使胰岛素是 1 型糖尿病中主要自身抗原的概念变得更加复杂。
Insulin is a major autoantigen in islet autoimmunity and progression to type 1 diabetes. It has been suggested that the insulin B-chain may be critical to insulin autoimmunity in type 1 diabetes. INS-IGF2 consists of the preproinsulin signal peptide, the insulin B-chain, and eight amino acids of the C-peptide in addition to 138 amino acids from the IGF2 gene. We aimed to determine the expression of INS-IGF2 in human pancreatic islets and autoantibodies in newly diagnosed children with type 1 diabetes and controls. INS-IGF2, expressed primarily in beta cells, showed higher levels of expression in islets from normal compared with donors with either type 2 diabetes (p = 0.006) or high HbA1c levels (p < 0.001). INS-IGF2 autoantibody levels were increased in newly diagnosed patients with type 1 diabetes (n = 304) compared with healthy controls (n = 355; p < 0.001). Displacement with cold insulin and INS-IGF2 revealed that more patients than controls had doubly reactive insulin-INS-IGF2 autoantibodies. These data suggest that INS-IGF2, which contains the preproinsulin signal peptide, the B-chain, and eight amino acids of the C-peptide may be an autoantigen in type 1 diabetes. INS-IGF2 and insulin may share autoantibody-binding sites, thus complicating the notion that insulin is the primary autoantigen in type 1 diabetes.