Autoimmunoreactive IgGs from patients with postural orthostatic tachycardia syndrome
Autoimmunoreactive IgGs from patients with postural orthostatic tachycardia syndrome
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DOI：
10.1002/prca.201200049
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发表时间：
2012-12-01
影响因子：
2
通讯作者：
Lee, Hon-Chi
中科院分区：
文献类型：
--
作者：
Wang, Xiao-Li;Chai, Qiang;Lee, Hon-Chi
目的：自身抗体与心血管疾病和心律失常的发病机制有关。在这项先导性研究中，我们检验了体位性直立性心动过速综合征(POTS)患者存在自身抗体的假设。实验设计：7名对照受试者(6名女性：1男性，平均年龄36.1岁)和10名诊断为POTS的患者(7名女性：3男性，平均年龄35.1岁)提供知情同意和30毫升静脉血。结果：检测到18个针对患者IGG的免疫反应阳性的蛋白质点，从凝胶中切下它们，经胰酶消化后，用纳米LC-电喷雾MS/MS分析，鉴定出40个独特的蛋白质，包括与心肌肥厚(Mimecan，myozenin)、心脏重塑(Periostin)、心肌病(Desmin，Desmoplakin)、细胞存活(Laminin)、结构完整性(细丝素)、伴侣蛋白(晶体，HSP70)、线粒体酶和通道蛋白相关的蛋白质。独创性通路分析显示多个通路参与，包括调节能量代谢、氧化还原、纤维化、心肌肥大和退行性变的通路。结论和临床相关性：POTS患者中存在自身抗体。这些自身抗体与多种心脏蛋白发生交叉反应，并可能导致心脏功能的改变。在这些患者中，自身免疫的致病机制有待进一步探讨。
Purpose: Autoantibodies are implicated in the pathogenesis of cardiovascular diseases and cardiac arrhythmias. In this pilot study, we tested the hypothesis that autoantibodies are present in patients with postural orthostatic tachycardia syndrome (POTS).Experimental design: Seven control subjects (6 F: 1 M, average age 36.1 years) and ten patients with the diagnosis of POTS (7 F: 3 M, average age 35.1 years) provided informed consent and 30 mL of venous blood. Human heart membrane proteins were resolved by 2DE and immunoblotted against purified IgGs from controls and patients.Results: Eighteen protein spots immunoreactive specifically against patient IgGs were detected and they were excised from gels, trypsin-digested, and analyzed by nanoLC-electrospray MS/MS. Forty unique proteins were identified and these include proteins that are associated with cardiac hypertrophy (mimecan, myozenin), cardiac remodeling (periostin), cardiomyopathy (desmin, desmoplakin), cell survival (laminin), structural integrity (filamin), chaperone proteins (crystalline, HSP70), mitochondrial enzymes, and channel proteins. Ingenuity Pathway Analysis showed multiple pathways were involved including those that regulate energy metabolism, redox, fibrosis, cardiac hypertrophy, and degeneration.Conclusions and clinical relevance: Autoantibodies are present in patients with POTS. These autoantibodies cross-react with a wide range of cardiac proteins and may induce alterations in cardiac function. Autoimmune pathogenetic mechanisms should be further explored in these patients.