Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia
Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia
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DOI：
10.1182/blood-2010-05-286161
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发表时间：
2010-12-02
期刊：
影响因子：
20.3
通讯作者：
Holland, Steven M.
中科院分区：
文献类型：
--
作者：
Burbelo, Peter D.;Browne, Sarah K.;Holland, Steven M.
胸腺恶性肿瘤患者的自身免疫发生率高，导致各种自身免疫性疾病，最常见的是由抗乙酰胆碱受体自身抗体引起的重症肌无力。还描述了高比率的细胞因子自身抗体，尽管这些抗细胞因子自身抗体的流行率、谱和功能性定义不清楚。为了更好地了解抗细胞因子自身抗体的存在和功能，我们创建了荧光素酶免疫沉淀系统面板，以搜索针对39种不同细胞因子的自身抗体，并检查了对照组（n = 30）和胸腺瘤形成患者（n = 17）的血浆。在该筛选中，我们的患者显示出统计学升高，但对39种细胞因子中的16种具有高度异质性的免疫反应性。部分患者出现多种细胞因子的自身抗体。功能测试证明，针对干扰素-α、干扰素-β、白细胞介素-1 α（IL-1 α）、IL-12 p35、IL-12 p40和IL-17 A的自身抗体在体外具有生物阻断活性。所有机会性感染患者均显示多种抗细胞因子自身抗体（范围3 - 11），表明抗细胞因子自身抗体可能在胸腺恶性肿瘤患者机会性感染的发病机制中起重要作用。本研究在www.example.com上注册为NCT 00001355。（血。2010; 116（23）：4848 - 4858）
Patients with thymic malignancy have high rates of autoimmunity leading to a variety of autoimmune diseases, most commonly myasthenia gravis caused by anti-acetylcholine receptor autoantibodies. High rates of autoantibodies to cytokines have also been described, although prevalence, spectrum, and functionality of these anti-cytokine autoantibodies are poorly defined. To better understand the presence and function of anti-cytokine autoantibodies, we created a luciferase immunoprecipitation system panel to search for autoantibodies against 39 different cytokines and examined plasma from controls (n = 30) and patients with thymic neoplasia (n = 17). In this screen, our patients showed statistically elevated, but highly heterogeneous immunoreactivity against 16 of the 39 cytokines. Some patients showed autoantibodies to multiple cytokines. Functional testing proved that autoantibodies directed against interferon-alpha, interferon-beta, interleukin-1 alpha (IL-1 alpha), IL-12p35, IL-12p40, and IL-17A had biologic blocking activity in vitro. All patients with opportunistic infection showed multiple anti-cytokine autoantibodies (range 3-11), suggesting that anti-cytokine autoantibodies may be important in the pathogenesis of opportunistic infections in patients with thymic malignancy. This study was registered at http://clinicaltrials.gov as NCT00001355. (Blood. 2010;116(23):4848-4858)