14-3-3 in Thoracic Aortic Aneurysms: Identification of a Novel Autoantigen in Large Vessel Vasculitis.
14-3-3 in Thoracic Aortic Aneurysms: Identification of a Novel Autoantigen in Large Vessel Vasculitis.
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DOI：
10.1002/art.39130
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发表时间：
2015-07
期刊：
影响因子：
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通讯作者：
Hoffman GS
中科院分区：
文献类型：
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作者：
Chakravarti R;Gupta K;Swain M;Willard B;Scholtz J;Svensson LG;Roselli EE;Pettersson G;Johnston DR;Soltesz EG;Yamashita M;Stuehr D;Daly TM;Hoffman GS
大血管血管炎是一组以大血管损伤和解剖改变为特征的自身免疫性疾病，包括主动脉及其分支血管。疾病病因尚不清楚。本研究从左心室患者的主动脉根部、升主动脉和主动脉弓手术标本中确定病变血管壁内的抗原靶点，包括巨细胞性大动脉炎、大动脉炎和孤立性局灶性大动脉炎。胸主动脉瘤标本和自体血液均取自接受主动脉重建手术的患者。主动脉蛋白提取自LVV患者和年龄、种族和性别匹配的非炎症性动脉瘤疾病对照。共有108份来自LVV患者、匹配的对照组和抗核抗体、不同形式的血管炎或败血症的对照组的血清样本进行了检测。108份血清样本和22份主动脉组织样本的评估结果显示，78%的LVV患者产生了抗14-3-3蛋白抗体(93.7%的特异性)，而对照组则较少产生抗体(6.7%)。左心室病患者血清中含有足以免疫沉淀14-3-3蛋白(S)的自身抗体。在7种14-3-3亚型中有3种在左心室患者的主动脉标本中表达上调，2种亚型(ε和ζ)在左心室中具有抗原性。这是第一次使用无菌、快速冷冻的胸主动脉活检标本来鉴定左心室自身抗原的研究。我们的发现表明78%的左心室患者对14-3-3蛋白有抗体反应(S)。这些抗体和14-3-3蛋白在LVV发病机制中的确切作用值得进一步研究。
Large vessel vasculitides (LVV) are a group of autoimmune diseases characterized by injury to and anatomic modifications of large vessels, including the aorta and its branch vessels. Disease etiology is unknown. This study was undertaken to identify antigen targets within affected vessel walls in aortic root, ascending aorta, and aortic arch surgical specimens from patients with LVV, including giant cell arteritis, Takayasu arteritis, and isolated focal aortitis. Thoracic aortic aneurysm specimens and autologous blood were acquired from consenting patients who underwent aorta reconstruction procedures. Aorta proteins were extracted from both patients with LVV and age-, race-, and sex-matched disease controls with noninflammatory aneurysms. A total of 108 serum samples from patients with LVV, matched controls, and controls with antinuclear antibodies, different forms of vasculitis, or sepsis were tested. Evaluation of 108 serum samples and 22 aortic tissue specimens showed that 78% of patients with LVV produced antibodies to 14-3-3 proteins in the aortic wall (93.7% specificity), whereas controls were less likely to do so (6.7% produced antibodies). LVV patient sera contained autoantibody sufficient to immunoprecipitate 14-3-3 protein(s) from aortic lysates. Three of 7 isoforms of 14-3-3 were found to be up-regulated in aorta specimens from patients with LVV, and 2 isoforms (ε and ζ) were found to be antigenic in LVV. This is the first study to use sterile, snap-frozen thoracic aorta biopsy specimens to identify autoantigens in LVV. Our findings indicate that 78% of patients with LVV have antibody reactivity to 14-3-3 protein(s). The precise role of these antibodies and 14-3-3 proteins in LVV pathogenesis deserves further study.