自身炎症性疾病

自身炎症性疾病是一组以发热为突出表现的常染色体遗传病,发病率低,主要由基因突变导致细胞因子改变,最终引起炎症反应。本文对国内外有关自身炎症性疾病发病机制的研究进行综述,为自身炎症性疾病提供有针对性的、有效的治疗手段。     

AIM2炎症小体在自身免疫性疾病发病中的作用研究进展

黑色素瘤缺乏因子2(AIM2)是AIM2炎症小体的重要组成部分。AIM2主要定位在细胞质中,与胞质中的双链DNA结合后,招募凋亡相关斑点样蛋白和半胱天冬酶1(Caspase-1)前体在内的凋亡相关蛋白,诱导Caspase依赖性的炎症小体形成,促使Caspase-1激活及IL-1β成熟与分泌,启动自身免疫反应。AIM2介导的免疫反应异常激活可导致免疫相关疾病,例如类风湿关节炎、系统性红斑狼疮、原发性干燥综合征、银屑病、白塞病等。在自身免疫疾病中,自身或外来DNA的异常累积可以激活AIM2炎症小体,释放致炎因子,参与炎症反应。因此,调控AIM2炎症小体活性,可发挥免疫保护作用,并阻止组织损伤及限制自身免疫反应。     

弓形虫感染与自身免疫性疾病关系的研究进展

弓形虫感染人体后,尤其是免疫低下或免疫抑制的患者,常造成严重损害.在众多疾病、尤其是自身免疫性疾病患者中,弓形虫感染率非常高,欧洲国家弓形虫抗体的阳性率在10％～80％不等,我国弓形虫抗体的阳性率在0.3％～10.0％.弓形虫感染与某些自身免疫病的发病密切相关,很多研究表明,自身免疫性疾病患者的弓形虫感染率显著高于对照组.也有动物实验证实弓形虫感染有助于保护机体,延缓疾病的进展.该文就弓形虫感染的机制和弓形虫感染与自身免疫性疾病的关系作一综述.     

心房颤动与自身免疫性疾病相关性的研究进展

心房颤动是一种常见的心律失常,心房颤动的发生与心房重构及炎症反应密切相关.自身免疫性疾病是一种全身性免疫炎症性疾病,可并发包括心房颤动在内的各种心血管疾病.近年来,大量关于自身免疫性疾病与心房颤动发生关系的研究结果表明,自身免疫性疾病与心房颤动的发生具有明显的相关性.本文就心房颤动与自身免疫性疾病相关性的研究进展进行了...     

自身炎症性疾病和自身免疫病

自身炎症性疾病(autoinflammatory disease,AID)与自身免疫病(autoimmune disease,AD)之间的关系近年来逐渐引发关注。AID和AD存在许多相似的特征,如两者病理过程都针对自身组织;两者都是系统性疾病;包括单基因疾病和多基因疾病;两者都是某些基因易感性个体免疫系统的慢性激活最终导致组织炎性。但是,两组疾病也存在不少差异,如AID是由于固有免疫系统直接导致组织炎性反应,其中炎性体失调发挥了关键作用;而AD是由于固有免疫激活适应性免疫而导致炎性反应和器官损伤,其中适应性免疫起到了重要作用,炎性体在AD发病中的作用尚未阐明;AID与AD不同,通常没有自身抗体或抗原特异性T淋巴细胞,参与炎性反应损伤过程的主要是单核巨噬细胞,而非T、B淋巴细胞。尽管AID和AD现在被划分为两组疾病,但更可以被看作是一大组疾病谱。     

泌乳素与自身免疫性疾病的研究进展

泌乳素(PRL)具有300多种独立的生物活性。其生理功能包括生殖、内分泌与代谢、维持水电解质平衡、促进生长发育,以及免疫调节和免疫保护功能等。近10年来,PRL与免疫系统之间的相互关系得到了阐述。PRL不仅能由垂体前叶分泌,而且垂体前叶以外的免疫细胞等也能够分泌PRL。内分泌、旁分泌和自分泌的PRL通过与泌乳素受体(PRL-R)结合,影响着靶细胞的生长、增殖和分化。自身免疫性疾病常伴有高泌乳素血症,推测PRL对人类的免疫调节起着重要的作用。     

基因芯片与自身免疫性疾病

基因芯片技术是 90年代兴起的一项前沿生物技术 ,它将生物学中许多不连续的分析过程连续化 ,并使其微型化 ,具有无可比拟的高效、快速和多参量的特点 ,是传统的生物技术如检测、杂交、分型和ＤＮＡ测序的一次重大创新和突破。美国《科学》杂志把基因芯片评为 1998年世界十大科技突破之一。《财富》杂志给予基因芯片极高的评价 ,认为微处理机在本世纪使我们的经济结构发生了根本改变 ,给人类带来了巨大财富 ,改变了我们的生活方式。然而 ,基因芯片给人类带来的影响可能会更大 ,它可能从根本上改变医学行为和我们的生活质量 ,从而改变世界的面…     

自身免疫性疾病与发热

自身免疫性疾病是由于机体自身免疫反应导致的一大组疾病,其临床表现复杂多样,是导致发热的常见原因。 与感染、肿瘤性疾病一样,自身免疫性疾病是发热的重要鉴别诊断。不同自身免疫性疾病具有特征性临床表现,诊 断需要根据临床表现、自身抗体、影像及病理检查综合确立。治疗过程中应密切观察体温变化,及时调整治疗方案。     

自然杀伤细胞及其与自身免疫性疾病的关系

自然杀伤细胞（natural killer cell，NK）主要来源于大颗粒淋巴细胞，占全血淋巴细胞的10％～15％左右，是先天性免疫系统的重要组成部分。NK细胞在机体抗御感染和肿瘤免疫中起重要作用。近年来，有关NK细胞与其它免疫细胞相互作用的研究日趋增多；NK细胞在自身免疫性疾病中的作用也逐渐受到重视。本文针对NK细胞的相关研究进展作一综述。     

T2DM动脉粥样硬化是一种慢性自身免疫性疾病

2型糖尿病(T2DM)患者动脉粥样硬化(AS)发生的自身免疫反应机制目前备受关注。多种免疫细胞(主要是CD3^ CD4^ T细胞，还有少数树突状细胞和肥大细胞)、细胞因子及抗体等通过与血管内皮细胞表达的各种粘附分子，如血管细胞粘附分子(VCAM)—1、细胞间粘附分子(ICAM)—1结合，参与T2DM患者AS斑块的形成。临床上目前虽无法检测到与AS发生、发展有关的独特性T细胞克隆，但通过检测血液中VCAM—1、ICAM—1以及几种自身抗原及其抗体，如热休克蛋白、氧化低密度脂蛋白(oxLDL)的变化可间接预测T2DM患者AS的发生、发展。     

固有免疫介导的炎症反应在动脉粥样硬化发病机制中的研究进展

动脉粥样硬化是常见慢性心脑血管疾病的病理基础,其病变始于血管内皮细胞构成的天然屏障功能障碍,由各种损伤因子影响内皮细胞Caspase-1/Sirt1/AP-1、SREBP2/NOX2/NLRP3、KLF2/FoxP1/NLRP3、NFAT5/NLRP3等通路信号转导、相关炎症基因表达,激活内皮细胞,继而单核细胞浸润主动脉壁内膜下并分化为巨噬细胞,引起相应内皮激活的固有免疫反应,在NLRP3/ASC/Caspase-1炎性小体途径激活后,使促炎症细胞因子IL-1β、IL-18释放增加,介导下游炎症因子、趋化因子等表达增加,促进动脉粥样硬化炎症反应;血管壁持续慢性炎症反应使血管平滑肌细胞表型转变,促进动脉粥样硬化斑块形成,还使斑块成分发生改变、易损性增加,斑块微钙化则增加了斑块处血管应力,破裂危险增加。本文综述了固有免疫介导的动脉粥样硬化炎症机制研究现状,为动脉粥样硬化抗炎药物研发提供思路以及促进抗动脉粥样硬化研究的实验设计。     

Statins and autoimmune diseases

Inhibitors of 3‐hydroxy‐3methylglutaryl coenzyme A (HMG‐CoA) reductase or statins are effective lipid lowering drugs. The lipid lowering activity is mainly achieved through reduction of cholesterol synthesis and up‐regulation of low density lipoprotein receptors that in turn clear low density lipoproteins and low density lipoprotein precursors from the blood. HMG‐CoA reductase competitively blocks mevalonate, the enzyme reaction product that is the precursor not only of cholesterol but also of several non‐steroidal isoprenoid compounds. Isoprenoids allow the attachment to the cell membrane of signalling proteins involved in various cell functions; their inhibition explains the so‐called pleiotropic effects of statins, which include anti‐inflammatory, anticoagulant and immunomodulatory properties. Such pleiotropic activities have been suggested to justify the benefits of statin therapy besides the simple reduction in plasma cholesterol levels. Accelerated atherosclerosis has been reported in several autoimmune rheumatic diseases. Non‐traditional risk factors for atherosclerosis, such as inflammation, immune‐mediated responses and thrombophilia, have been suggested to play a major role in sustaining premature atherosclerosis in autoimmune rheumatic diseases. This review focuses on the potential use of statins as a new therapeutical tool for treating autoimmune rheumatic diseases based on their antiatherosclerotic activity and on their pleiotropic effect on inflammation, haemostasis and the immune responses.     

Antineutrophil cytoplasmic autoantibodies in autoimmune liver and inflammatory bowel diseases

Abstract: Perinuclear antineutrophil cytoplasmic autoantibodies have been described in inflammatory bowel diseases and in primary sclerosing cholangitis. Because the data concerning their occurrence are conflicting, we have used indirect immunofluorescence on ethanol-fixed neutrophils to test the sera from a large population of 382 patients with various liver and digestive diseases: in particular, from 27 patients with primary sclerosing cholangitis, 105 patients with autoimmune chronic active hepatitis, 30 patients with primary biliary cirrhosis and 124 patients with inflammatory bowel disease. The prevalence of the perinuclear antineutrophil cytoplasmic autoantibodies was 37% in ulcerative colitis and 15% in Crohn's disease. They would not be helpful in the differential diagnosis between these two inflammatory bowel diseases. Within the group of autoimmune liver diseases, perinuclear antineutrophil cytoplasmic autoantibodies were detected in 44% of sera from patients with primary sclerosing cholangitis and in 36% of sera from patients with type I autoimmune active hepatitis, but not in primary biliary cirrhosis. When primary sclerosing cholangitis was associated with an inflammatory bowel disease, the prevalence of these autoantibodies was 60%. They were 88% specific for primary sclerosing cholangitis and 86% specific for type I autoimmune active hepatitis. Despite their moderate sensitivity and specificity in primary sclerosing cholangitis, they remain the only serologic marker of this autoimmune liver disease. Moreover, they turned out to be a more sensitive marker for inflammatory bowel disease with associated primary sclerosing cholangitis     

Anti-cytomegalovirus antibodies and other atherosclerosis risk factors in patients with cardiovascular diseases

Objective To determine anti-cytomegalovirus (CMV) antibodies along with anti-Chlamydia pneumoniae (CP)antibodies in comparison with inflammatory markers and other risk factors of atherosclerosis in patients with selected cardiovascular diseases(CVD).Methods A total of 228 patients with coronary heart disease (CHD) and/or hypertension (HT), and those who underwent reconstructive vascular surgery (RVS) on carotids or abdominal aorta were tested for the presence of anti-CMV IgG and IgM antibodies as well as for anti-CP IgA antibodies, C-reactive protein (CRP),and interleukin-6 (IL-6). Other risk factors for atherosclerosis, namely age, gender,smoking, hypercholesterolemia, and diabetes mellitus were also analyzed. Results Anti-CMV IgG antibodies were found in 204 patients sera (89.5%),compared with 46 positive of 68 sera in the controls (67.6%), whereas anti-CMV IgM antibodies were detected in 4 of 54 sera of patients tested (7.4%), but not in the controls. The highest proportion of positive sera with not only anti-CMV IgG antibodies (95.6.7%),but also anti-CP IgA antibodies (78.3%), IL-6 (84.8%) and CRP (97.8%), was observed in patients with RVS. The results obtained corresponded to age, hypercholesterolemia, and diabetes. Conclusions The presence of anti-CMV antibodies together with antibodies to CP and markers of inflammation (CRP and IL-6) in our study was associated with CVD, primarily in elderly patients who underwent RVS.     

Involvement of midkine in autoimmune and autoinflammatory diseases

Abstract

Midkine (MK) is a heparin-binding growth factor that markedly expressed during embryogenesis but downregulated to inconsiderable levels in healthy adults. However, MK is upregulated during tissue repair and in many pathologic conditions, mostly malignancies and inflammatory diseases. MK promotes a number of functions in target cells such as migration, proliferation, survival, growth, reproduction and repair, angiogenesis, and gene expression. It acts as a pro-inflammatory cytokine and contributes to chronic inflammation via promoting chemotaxis and tissue infiltration of neutrophils and macrophages. Furthermore, MK upregulated the production of various inflammatory mediators (i.e. interleukin (IL) 6 and IL8). Recent studies have demonstrated strong evidence that MK is involved in the onset and progression of autoimmune rheumatic diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren’s syndrome (SS) and other autoimmune conditions such as multiple sclerosis (MS). Additionally, it has been shown that MK is overexpressed in two major clinically defined forms of inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), which are classified as autoinflammatory diseases. Taken together, MK is involved in the pathogenesis of autoimmune and autoinflammatory diseases and may serve as an indicator and biomarker in these conditions. Furthermore, MK inhibitors are expected to contribute in the management of these diseases.     

低氧诱导因子在心血管疾病中的研究进展

低氧诱导因子(HIF)为缺氧敏感性转录因子,是细胞对缺氧反应的主要调节因子,可诱导炎症、脂质代谢、内皮功能障碍、血管平滑肌细胞(VSMC)增殖,调控心血管疾病(CVD)的发生发展。该文综述了近年来HIF在CVD中的作用及作用机制的研究进展,讨论HIF对血管构成细胞类型的作用及机制以及与CVD发生发展之间的关系,可为解析CVD的发病机制和发现新的治疗靶点提供参考,旨在为进一步了解HIF在CVD发病机制中的作用及机制提供理论参考,并为设计靶向HIF的新型有效治疗药物提供依据。     

I型自身免疫性胰腺炎的研究进展

自身免疫性胰腺炎（AIP）是逐渐被认识的慢性胰腺炎的一种类型,与其他类型的慢性胰腺炎有明显的不同。随着2001年发现AIP患者血清IgG4含量明显增高,这个现实被广泛的接受。1型AIP与2型AIP不同。2％的慢性胰腺炎为1一AIP,成人男性患者居多。患者通常由于胰头的增大或胆管壁增厚所致梗阻性黄疸,通过血清学、影像学和组织学与胰腺癌鉴别。血清IgG4水平的增高是最为敏感和特异性的表现。影像学的表现为胰管的不规则狭窄,胰腺弥散性或局灶性的扩大及胰周可见环形的囊壳样影,以及影像延迟期强化。组织学显示大量的dxDt问质表现为致密的纤维化伴席纹状、炎细胞浸润,闭塞性静脉炎和lgG4阳性细胞数量增加。激素治疗疗效明显是另外的特征,在初治的2～3周血清学和影像学明显改善。基于同步或不同步的伴有多器官的损伤,1一AIP也被认为是一种IgG4相关全身性疾病。至今有一些与1一AIP相关的自身免疫性抗原被鉴定,但IgG4在此病中的作用是肯定的。     

调节性T细胞在动脉粥样硬化发生机制中作用的研究进展

动脉粥样硬化(As)是动脉血管壁的一种慢性炎症性病变,相关免疫机制参与其发生、发展过程。调节性T细胞(Treg)是一种具有独特免疫调节功能的T淋巴细胞亚群,大量证据表明,Treg的数量变化和功能障碍与As的发病机制密切相关。文章简要阐述Treg在As发展中的作用机制,并介绍了Treg作为一种新型药物治疗靶点在预防和治疗As中的最新研究进展,以期对动脉粥样硬化性疾病的发生与防治提供新思路。     

自身免疫性肝病重叠综合征的临床诊治进展

自身免疫性肝病是血清中出现相关的自身抗体和免疫球蛋白,并由此引起相应的肝脏病理损伤和肝功能生物化学异常的一组自身免疫性疾病,包括自身免疫性肝炎(AIH)、原发性胆汁性肝硬化(primary biliary cirrhosis,PBC)和原发性硬化性胆管炎(primary sclerosing cholangitis,PSC).这3种疾病都有其各自典型的临床表现和血清生物化学、免疫学及病理学特征,然而,在许多情况下,患者的临床特征往往不那么典型,而表现为兼有以上3种中2种疾病的特征,我们称之为重叠综合征.