杀伤细胞免疫球蛋白样受体基因多样性与自身免疫性甲状腺病关联性的研究
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摘要
背景:自身免疫性甲状腺病(Autoimmune thyroid dieases,AITD)是一组器官特异性自身免疫性疾病。自身免疫性甲状腺病主要包括Graves病(Graves disease,GD)、桥本甲状腺炎(Hashimoto's thyroiditis,HT)、特发性粘液性水肿(idiopathic myxedema,IM)、Graves眼病(Graves ophthalmopathy,GO)和产后甲状腺炎(postpartum thyroiditis,PPT)等疾病。自身免疫性甲状腺病是人群中最常见的自身免疫性紊乱之一,在女性患病率2%~4%,男性约1%。其中Graves病和桥本甲状腺炎属于内分泌系统的最常见的自身免疫性疾病,在人群中的发病率逐年增加,是我国的常见病和多发病,严重危害人民群众的健康。
     目前认为,自身免疫性甲状腺病属于T细胞功能紊乱所致的一类器官特异性自身免疫性疾病,它的发生是遗传、环境因素共同作用的结果。作为器官特异性自身免疫性疾病,免疫机制在自身免疫性甲状腺病的发病中有着重要的作用。研究认为,在自身免疫性甲状腺病的发生机制中,存在抑制性T细胞功能缺陷的遗传背景,在各种环境因素的作用下,自身免疫耐受被破坏,辅助性T细胞异常激活,从而引发一系列针对甲状腺的自身免疫反应,既有细胞免疫,也有体液免疫的参与,包括自身抗体的产生,细胞毒性T淋巴细胞和NK细胞的功能失调,炎性细胞因子的大量产生释放,以及细胞凋亡的失控等免疫紊乱,最终导致甲状腺功能和结构的改变。
     自身免疫性甲状腺病中的不同疾病可在同一个体同时或先后出现,提示它们之间可能存在共同的发病基础:但疾病的临床表现和病理改变又各有特点,故又可能各有不同的发病机制。
     Graves病和桥本甲状腺炎是自身免疫性甲状腺病中最主要的两种疾病。它们
Background: Autoimmune thyroid diseases (AITD), including Graves disease (GD), Hashimoto's thyroiditis (HT), idiopathic myxedema (IM), postpartum thyroiditis (PPT), and thyroid-associated orbitopathy (TAO), are organ-specific autoimmune diseases. AITD are the most common autoimmune disorders in population, affecting between 2% and 4% of women and up to 1% of men. Graves disease and Hashimoto's thyroiditis are the main forms of AITD, the prevalence of them increases year and year, and they are the common endocrine diseases in our country.
    AITD are organ-specific T-cell mediated autoimmune diseases. Widely accepted model for the pathogenesis of AITD suggests that each subject has a background inherited predisposition to autoimmunity, with additional environmental factors that trigger or contribute to the development of the disease. As organ-specific autoimmune diseases, immunological mechanism plays an important role in the pathogenesis of AITD. Evidence shows that subject has background inherited defect of suppressor T cells (Ts) in the pathogenesis of AITD. Environmental factors contribute to the breakdown of immunological self-tolerance that results in the presentation of host autoantigens and expansion of autoreactive lymphocyte clones which leads to a series of autoimmune response to thyroid autoantigens. Not only cellular immunity but also hormonal immunity participate in the progress of AITD, including production of autoantibodies, abnormal immune activity of CTL and NK cells, release of excessive
引文
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