CD40-CD40配体共刺激通路在甲状腺相关性眼病发病中作用研究进展

甲状腺相关性眼病(thyroid-associated ophthalmopathy,TAO)是器官特异性自身免疫性疾病,其发病机制涉及T细胞对几种自身抗原的耐受丧失及以T细胞为主的免疫细胞不适当活化。T细胞活化需要识别共刺激信号,其中CD40-CD40L作为T细胞活化的共刺激信号之一,在TAO的发病机制中起重要作用。本文就CD40-CD40L分子细胞学特征、功能及近年关于其在TAO发病机制中的作用研究进展作一综述。     

葡萄膜和视网膜损伤时的自身免疫反应

近年来研究免疫机制在眼病中的作用,尤其是血管、角膜和视网膜炎性疾病等特别受到重视。目前的研究主要有以下几方面:寻找和分离有活性的自身抗原,改进提取和纯化的方法,研究其致病的特性;用各种葡萄膜炎实验模型研究自身变态反应性疾病的发病机理;核准免疫学实验,以便研究临床上炎症性眼病的发病机制,进行病因诊断和预后估计,研究用视网膜自身抗原进行治疗的可能性。一、致病的视网膜抗原在豚鼠、家兔和大鼠的实验中发现,注射一     

肿瘤相关性视网膜病变的研究进展

肿瘤相关性视网膜病变(cancer-associated retinopathy,CAR)是一种与肿瘤有关的视网膜变性疾病,其发病机制认为是肿瘤抗原诱导机体产生抗视网膜蛋白的抗体而引起的自身免疫性疾病,而非眼部原发肿瘤的占位压迫或全身其他部位肿瘤转移所引起.CAR对视功能的影响很大,目前该病已逐渐被眼科医师所认识.本文从CAR的发病机制、临床表现、诊断及鉴别诊断、治疗方面作一综述.     

微生物感染是否总是有害?

微生物感染(包括寄生虫感染)可以打破机体自身免疫耐受,导致免疫系统功能紊乱,从而诱发机体出现自身免疫症状.分子模拟作为外来抗原与自身抗原之间的一种常见现象,被认为在自身免疫性疾病的发病中起着至关重要的作用.然而,大量研究表明,许多微生物中的模拟抗原肽非但不会诱导机体出现自身免疫症状,甚至还可以作为一种天然的修饰抗原肽,对再次受到相似抗原入侵的机体从抗体水平或者T细胞水平起到一定的保护作用.本文立足于分子模拟的机制,综述了微生物感染后被感染机体可能的预后.     

甲状腺相关眼病免疫学发病机理的研究进展

甲状腺相关眼病目前被认为是一种与Graves病关系密切的器官特异性自身免疫性疾病,其具体发病机制至今仍未明确。已有研究发现:自身抗原、眶内成纤维细胞、免疫细胞、细胞因子及免疫介质等都是该病发病过程中的重要因素。     

人促甲状腺激素受体基因真核表达质粒的构建

甲状腺相关眼病（thyroid-associated ophthahnopathy,TAO）是一种与自身免疫性甲状腺疾病密切相关,且累及眼眶组织的慢性器官特异性自身免疫性疾病。目前普遍认为人促甲状腺激素受体（thyroid stimulating hormone receptor,TSHR）是TAO发病的最主要自身抗原。通过人TSHR构建合适的TAO动物模型有助于TAO的深入研究。但存在于甲状腺细胞膜的人TSHR蛋白量较少,且结构不稳定,因此有必要对其进行分子克隆,为构建TAO动物模型及进一步研究其发病机制和防治措施奠定基础。     

内眼手术后患者血清晶状体抗体与视网膜可溶性抗体的动态变化

内眼手术,可引起晶状体抗原和视网膜可溶性抗原的释放,刺激机体产生自身免疫反应,并在一定的条件下引起自身免疫性疾病。本实验用ELISA检测白内障、青光眼和视网膜脱离三种手术前后晶状体抗体和视网膜可溶性抗体的滴度,动态观察滴度变化,探讨眼自身抗原在人体的免疫反应规律,以及与色素膜炎的关系。     

甲状腺相关眼病与细胞凋亡

甲状腺相关眼病(TAO)是一种器官特异性自身免疫性疾病,与自身免疫性甲状腺功能亢进症(GD)密切相关。眼眶自身抗原的表达诱发机体免疫平衡状态紊乱,免疫功能活化,进而对眶内组织产生免疫损害。细胞凋亡是指在基因水平调控下的机体细胞的程序性死亡过程,Fas/FasL系统是介导细胞凋亡的最主要途径。研究表明,细胞凋亡在自身免疫性疾病发病过程中起重要作用。就甲状腺相关眼病与细胞凋亡以及二者的相互关系作一综述。     

与青光眼相关的自身抗体

免疫系统和青光眼的关系是近年来研究的热点之一,尤其是自身免疫性疾病与开角型青光眼（原发性开角型青光眼和正常眼压性青光眼）之间的关系。研究显示,青光眼患者特别是开角型青光眼患者,其血清或房水中存在自身抗体,或者其本身即患有自身免疫性疾病。青光眼患者在发病过程中是否触发了自身免疫性疾病,或自身免疫应答是否引起青光眼的机制之一（引起或促进青光眼病程发展）,尚在进一步研究中。     

与青光眼相关的自身抗体

免疫系统和青光眼的关系是近年来研究的热点之一,尤其是自身免疫性疾病与开角型青光眼(原发性开角型青光眼和正常眼压性青光眼)之间的关系.研究显示,青光眼患者特别是开角型青光眼患者,其血清或房水中存在自身抗体,或者其本身即患有自身免疫性疾病.青光眼患者在发病过程中是否触发了自身免疫性疾病,或自身免疫应答是否引起青光眼的机制之一(引起或促进青光眼病程发展),尚在进一步研究中.     

Oral tolerance for treating uveitis - new hope for an old immunological mechanism

Oral tolerance induction has evolved as an attractive approach for the treatment of autoimmune uveitis. This approach is effective and generally void of the side effects associated with conventional immunosuppression. Following uptake of soluble antigen via the gut mucosa a specific systemic tolerance is generated. Experimental autoimmune diseases such as uveitis can efficiently be treated when autoantigens are fed to animals. The immunological mechanisms of oral tolerance are not well understood but are thought to involve the recognition of tolerogenic epitopes, generation of suppressor T cells and altered regulation of selected cytokines. The dose, purity of the antigen (tissue extract vs. single peptide) and concomitant treatment with cytokines were evaluated with the aim to enhance oral tolerance. Immunomodulatory drugs can abrogate oral tolerance. This requires careful evaluation with respect to therapeutic approaches in patients. The first clinical trials for treatment of uveitis with oral retinal autoantigen or an HLA-peptide crossreactive with S-Antigen show a promising therapeutic effect and confirmed the safety of this approach.     

Nasal administration of retinal antigens suppresses the inflammatory response in experimental allergic uveoretinitis. A preliminary report of intranasal induction of tolerance with retinal antigens.

Current immunotherapy of posterior uveitis is non-specific and limited by drug toxicity and unpredictable relapses on therapy. Alternative modes of therapy being investigated using the rat model of experimental autoimmune uveoretinitis (EAU) have included the induction of tolerance with oral administration of milligram quantities of retinal antigens. In this preliminary report we demonstrate that tolerance to retinal antigens can be induced via the upper respiratory tract with microgram doses of antigen, preventing subsequent induction of EAU.     

High incidence of glucose intolerance in Vogt-Koyanagi-Harada disease

AIMS—To evaluate glucose tolerance of patients with Vogt-Koyanagi-Harada (VKH) disease before systemic corticosteroid therapy, and to assess changes brought on by treatment.METHODS—20 VKH patients with acute bilateral panuveitis were studied. 20 healthy adults and 11 Behçet''s disease patients with active uveoretinitis served as controls. A 75 g oral glucose tolerance test (OGTT) was given in the acute stage of ocular inflammation before systemic corticosteroid therapy. The OGTT was repeated in the convalescent stage of VKH disease in the patients with glucose intolerance before treatment. Insulin response was examined at the same time as the OGTT when possible.RESULTS—55% of VKH patients (11/20) showed glucose intolerance but no apparent insulin secretion deficiency was detected. Four of seven patients in the convalescent stage showed improvement of glucose tolerance. None of the normal controls or disease controls showed glucose intolerance.CONCLUSION—A high incidence of glucose intolerance was found in the acute stage of VKH disease. However, glucose intolerance improved in most cases after systemic corticosteroid therapy. It is possible that glucose intolerance seen in VKH patients may be related to the autoimmune inflammatory process of this disease.     

实验性自身免疫性葡萄膜炎T淋巴细胞亚群与Treg细胞的表达研究

目的　探讨实验性自身免疫性葡萄膜炎（ｅｘｐｅｒｉｍｅｎｔａｌａｕｔｏｉｍｍｕｎｅｕｖｅｉｔｉｓ,ＥＡＵ）新西兰兔模型外周血单个核细胞（ｐｅ-ｒｉｐｈｅｒａｌｂｌｏｏｄｍｏｎｏｎｕｃｌｅａｒｃｅｌｌｓ,ＰＢＭＣ）Ｔ淋巴细胞亚群的变化及其与疾病特征的相关性。方法　选取健康成年雄性新西兰大白兔４０只作为动物模型,用２０ｇ·Ｌ－１牛血清蛋白（ｂｏｖｉｎｅｓｅｒｕｍａｌｂｕｍｉｎ,ＢＳＡ）静脉注射和玻璃体内注射法建立ＥＡＵ模型,并观察模型眼炎症反应及ＰＢＭＣＴ淋巴细胞亚群特征。结果　ＣＤ４＋Ｔ细胞在ＥＡＵ兔的外周血中比例明显增加,且随时间的进展呈进行性增加,并与炎症反应呈正相关,相同的趋势可见于ＣＤ４＋／ＣＤ８＋Ｔ细胞比例。此外,Ｔｒｅｇ细胞趋势与ＣＤ４＋Ｔ细胞及ＣＤ４＋Ｔ／ＣＤ８＋Ｔ细胞比例相反,与炎症反应呈负相关。结论　ＣＤ４＋Ｔ细胞的优势性选择性克隆增殖及Ｔｒｅｇ细胞的降低有可能引发免疫功能紊乱并导致针对自身组织的免疫应答失去有效的负性调控,导致ＥＡＵ的发生及进行性加重。     

Plasma endothelin-1 levels depress optic nerve head circulation detected during the glucose tolerance test

Purpose To determine the relationship between the changes in optic nerve head (ONH) circulation and the level of plasma endothelin-1 (ET-1) during the glucose tolerance test (GTT). Methods Twenty-six healthy volunteers with normal GTT and 15 patients with mild hyperglycemia and abnormal GTT were studied. The ONH circulation [square blur rate (SBR) value], blood pressure, intraocular pressure (IOP), blood glucose, blood insulin and plasma ET-1 were determined before and every hour up to 3 h after an oral intake of 75 g of glucose. Results The SBR increased in the normal glucose tolerance group at all times during the GTT, but it decreased significantly in the abnormal glucose tolerance group (P < 0.05). Before the GTT, the plasma ET-1 level was not significantly different in the two groups; however, the level increased 1 h after the oral GTT in the abnormal glucose tolerance group (P < 0.05). No significant changes were observed in mean blood pressure or IOP. Conclusions ONH circulation increased after glucose intake in the normal glucose tolerance group and remained high even after the blood glucose level had returned to its baseline. The decrease in ONH circulation in the abnormal glucose tolerance group was attributed partly to the increased ET-1.     

Rat models of autoimmune uveitis

Experimental autoimmune uveitis (EAU) in Lewis rats is a well-established model for human uveitis. During the last years we used this model to demonstrate extraocular induction of uveitis by antigenic mimicry of environmental antigens with retinal autoantigen and investigated the migration and intraocular reactivation of autoreactive green fluorescent protein (GFP)+ T cells. We could also elaborate several differences between EAU induced with S-antigen peptide PDSAg or R14, a peptide derived from interphotoreceptor retinoid-binding protein, suggesting two differently regulated diseases in the same rat strain. R14-mediated EAU in Lewis rats has been shown to relapse, thus we have a new model to test therapeutic approaches in an ongoing immune response instead of just preventing disease. Finally, we show antigenic mimicry of PDSAg and an HLA-B peptide for oral tolerance induction. After the successful first therapeutic trial this approach will now proceed with international multicenter clinical trials.     

HLA-B27相关前葡萄膜炎的研究进展

HLA-B27阳性前葡萄膜炎是前葡萄膜炎最常见的类型,患者多为青壮年,反复发作,常引起一些并发症,严重影响视力,并可伴有其他系统性疾病。但其发病机制目前仍不清楚,尚无特效的治疗方法。近年来,建立了一些前葡萄膜炎动物模型,如内毒素诱导的前葡萄膜炎和HLA-B27转基因动物模型,并进行了一系列的研究。一些新的治疗方法在临床及动物实验中也取得了很好的疗效。就HLA-B27相关前葡萄膜炎的发病机制、流行病学、动物模型及一些新的治疗方法进行综述。     

Insulin resistance and atherosclerosis in branch retinal vein occlusion

PURPOSE: To investigate insulin resistance and atherosclerotic change in patients with branch retinal vein occlusion (BRVO). SUBJECTS: Sixty-three patients with BRVO, 859 age- and sex-matched control subjects without BRVO who received the 75-g oral glucose tolerance test (OGTT), and 53 control subjects, in whom carotid artery intima-media thickness (IMT) was measured by high-resolution ultrasonography, were included in this study. RESULTS: The area under the curve of immunoreactive insulin in plasma during the OGTT was higher in patients with BRVO than in control subjects without BRVO, both when comparing individuals with normal glucose tolerance (P=.013) and when comparing individuals with impaired glucose tolerance (P<.005). Patients with BRVO showed greater IMT than control subjects, but the differences were significant only in the group aged 50-59 years and in the group older than 70 years. CONCLUSIONS: Insulin resistance may play some role in the onset or progression of BRVO.     

调节性T细胞等关键免疫负向调节因子与自身免疫性葡萄膜炎相关性的研究进展

葡萄膜炎是由自身免疫系统紊乱导致的一种较常见的炎症性致盲性眼部疾病。目前,国内外学者的研究普遍认为,葡萄膜炎主要是由CD4^＋T细胞介导产生。CD4^＋T细胞可分为辅助性T细胞1(Th1)、辅助性T细胞2(Th2)、辅助性T细胞17(Th17)及调节性T细胞(Treg)四个亚群。既往研究主要集中于Th1、Th2及Th17细胞亚群。近年来,随着相关研究的不断深入,国内外学者发现,Treg细胞是负向调控葡萄膜炎的主要因素。Treg细胞能够抑制自身反应性T细胞的免疫反应、抑制传统T细胞的活化及促进某些抑制性细胞因子的分泌,从而在控制机体自身免疫性疾病的发生中发挥着重要作用。有学者研究发现,Treg细胞对维持机体的正常免疫耐受性具有十分重要的作用,它的数量及功能变化与许多免疫相关疾病的发生和发展有关。本文中笔者就Treg细胞与自身免疫性葡萄膜炎(EAU)的相关性研究进展进行综述。