重症肌无力与细胞因子

重症肌无力(MG)是一种自身免疫性疾病。研究表明细胞因子在MG发病过程中起重要作用。本文就近年来与MG发病及发展相关的细胞因子(干扰素、肿瘤坏死因子、转化生长因子、白细胞介素)作一综述。     

重症肌无力的发病机制

重症肌无力(MG)是一种神经-肌肉接头传递功能障碍的自身免疫性疾病。MG的发病机制主要涉及免疫因素和遗传因素。免疫因素包括多种致病抗体、细胞免疫、细胞因子、补体及胸腺等。随着免疫学研究的不断进展,MG的发病机制也有了更深入的研究。     

重症肌无力免疫学机制研究进展

重症肌无力(MG)是一种神经肌肉接头(NMJ)传递障碍的获得性自身免疫性疾病,发病机制主要以体液免疫为主、细胞免疫依赖及补体参与。研究表明,MG的发病与多种淋巴细胞及其亚群、抗体、补体及各种细胞因子之间复杂的相互作用有关。故了解MG的免疫学发病机制对MG的诊断及治疗有重大意义。     

重症肌无力患者血清Th1/Th2/Th17细胞因子的变化及意义

目的：分析重症肌无力（MG）患者血清CD4^＋ T细胞主要细胞因子的水平,探讨不同亚型CD4^＋ T细胞分泌的细胞因子在MG发病机制中的作用。方法：用ELISA测定93例MG患者和34名健康对照者血清中各项细胞因子（IL-2、IL-12、IFN-γ、TNF-α、IL-4、IL-10、IL-13和IL-17）的水平,分组行统计学分析。结果：与健康对照组相比,MG患者Th1细胞相关各细胞因子（IL-2、IL-12、IFN-γ及TNF-α）均明显升高,差异有统计学意义（P〈0.05）;Th2细胞相关的细胞因子IL-4、IL-10差异无统计学意义（P〉0.05）,仅IL-13水平升高;Th17细胞的细胞因子IL-17水平差异无统计学意义（P〉0.05）。MG眼肌型与全身型患者血清中各细胞因子水平的差异无统计学意义（P〉0.05）,在不同病程的MG患者中差异也无统计学意义（P〉0.05）。结论：Th1细胞因子在MG发病机制中发挥重要作用,而Th2细胞及其细胞因子在MG机制中的角色各异。     

重症肌无力发病相关基因多态性的研究进展

重症肌无力(MG)是一种神经肌肉接头传递功能障碍的自身免疫性疾病,其发病免疫机制尚未完全阐明,神经肌肉接头处其他抗体、抗原特异性T细胞、细胞因子、调节性T细胞等多种因素都与MG的发病机制有关,其中遗传因素在MG的发病中具有十分重要的作用.基因芯片技术可用于对疾病的相关基因进行筛选,并对疾病的分类、预后、治疗效果提供有用的信息.MG的易患基因及基因多态性的复杂性,目前在研究策略上还有待于进一步探索,现就近年来MG遗传学研究的进展综述如下.     

重症肌无力的有关遗传基因研究

本文主要介绍与重症肌无力(MG)发病有关的基因,如人类白细胞共同抗原、编码乙酰胆碱受体α亚单位的CHRNA1基因、编码胆碱酯酶的基因、编码乙酰胆碱受体结合蛋白的基因、编码骨骼肌特异性酪氨酸激酶的基因,以及与细胞凋亡有关的基因和某些细胞因子基因等,希望从基因水平认识MG发病机制,有关其基因治疗方法尚待研究。     

重症肌无力发病机制的研究进展

重症肌无力 (myastheniagravis,MG)是一种神经肌肉接头 (neuromuscularjunction,NMJ)传递功能障碍的自身免疫性疾病,其发病机制尚未完全阐明。传统观点认为MG的发病与乙酰胆碱受体自身抗体(AChR Ab)介导的体液免疫密切相关,但最近发现NMJ处其他抗体、抗原特异性T细胞、细胞因子、调节性T细胞、遗传因素等在MG的发病中也扮演了重要的角色。一、体液免疫临床上发现大约 80%的MG患者血清中能检测到AChR Ab,称为血清阳性重症肌无力 (seropositivemyastheniagravis,SPMG),而另外 20%的MG患者体内不能检测到AChR Ab,即所谓血清…     

微小RNA在重症肌无力免疫调节机制作用的研究进展

重症肌无力(MG)是一种由神经肌肉接头(neuromuscular junction,NMJ)传递障碍所致的获得性自身免疫性疾病,其发病机制主要以体液免疫为主,细胞免疫依赖及细胞因子、补体亦均参与其中。现有研究表明,微小RNA可能参与MG的发病机制,其分别通过对CD4+T系列细胞的调控作用促进炎性因子释放,对相关B细胞和补体的调控,以及对致病抗体乙酰胆碱受体(AChR)抗体和抗骨骼肌酷氨酸激酶(MuSK)抗体等分泌的调控,在MG发病中起着促进和调整作用。本文就微小RNA在MG中的上述三个作用进行综述。     

重症肌无力相关抗体研究进展

<正>重症肌无力(myasthenia gravis,MG)是一种由多种基因调控,多种抗体、免疫细胞、细胞因子、补体参与的自身免疫疾病,主要影响神经-肌头接头处(neuromuscular junction,NMJ)突触后膜上信号传导,多数是由乙酰胆碱受体抗体(acety-lcholine receptor antibody,AchR-Ab)介导,其确切发病机制仍然未明确[1]。MG最先在1672年,由英国Thomas Willis报道;Simpson于1960年报道该病与自身免疫功能障碍相关。与其他自身免疫疾病一样,MG易复发。对MG发病机制深入研究、提高诊断和治疗水平对于提高患者生活质量有重大意义。     

IL-18及其在重症肌无力中的研究进展

重症肌无力（myasthenia gravis，MG）是由乙酰胆碱受体抗体（AChRAb）介导的细胞免疫依赖的、补体参与的自身免疫性疾病。在MG免疫紊乱的研究中细胞因子网络失衡是目前研究的热点。白介素-18（IL-18）是近年来新发现的一种多效细胞因子，在免疫网络调节中具有重要作用。     

重症肌无力的免疫发病机制研究进展(英文)

重症肌无力是一种由抗乙酰胆碱受体的抗体介导的神经肌肉接头处的自身免疫病。其发病机制尚未阐明。自身抗体、淋巴细胞免疫调节紊乱、细胞因子表达失衡及系统因素在重症肌无力的发病机制中均起重要作用。本综述旨在探讨重症肌无力的免疫学发病机制。     

Primary progressive multiple sclerosis and generalized myasthenia gravis: an uncommon association

The co-occurrence of myasthenia gravis (MG) and multiple sclerosis (MS) is rare, and in all the described cases MS had a relapsing-remitting course and the diseases had a benign clinical evolution. We describe herewith a patient with primary progressive MS (PPMS) and generalized MG with severe clinical course. This is the first report on a case of PPMS associated to MG. Studies on the histology and pathogenesis show that neurodegeneration is predominant over inflammation in PPMS, even if cellular and humoral immune-mediated mechanisms are thought to maintain a crucial importance in the development and progression of this form of disease. In the present case, the detection of cerebrospinal fluid IgM oligoclonal bands support the hypothesis of a possible role of antibody-mediated immunity in PPMS and suggest that humoral immunity may take part in the concomitant development of both MS and MG.     

免疫抑制剂对重症肌无力病人T淋巴细胞亚型的影响

目的观察重症肌无力(MG)病人细胞免疫的异常改变和免疫抑制剂对重症肌无力(MG)病人的临床疗效及对T淋巴细胞亚型的影响。方法用许氏评分法观察60例MG病人的病情严重程度和免疫抑制治疗2个月后的临床疗效;采用直接免疫荧光染色和流式细胞仪技术测定60例病人和60名志愿健康者周围血中T淋巴细胞亚型的百分率,并测定糖皮质激素或环磷酰胺免疫抑制治疗前及治疗后2个月T淋巴细胞亚型的变化。结果未治疗MG组外周血中CD8 T淋巴细胞的百分率较正常对照组显著下降(P<0.01);CD4 T淋巴细胞的百分率和CD4 /CD8 T细胞的比例较正常对照组均显著升高(P<0.01)。经激素或环磷酰胺治疗2个月后MG组随着临床症状的改善,外周血中总T细胞(CD3 )和CD8的百分率较治疗前均显著升高(P<0.01;P<0.05);CD4 T淋巴细胞的百分率和CD4 /CD8 T细胞的比例较治疗前均显著下降(P<0.01)。结论MG病人有T淋巴细胞亚型的变化,免疫抑制治疗对T淋巴细胞亚群有明显影响,提示T淋巴细胞亚型的测定可为激素、环磷酰胺等免疫疗法提供一个客观的实验室指标,为判断疾病的转归提供实验依据。     

胸腺切除对重症肌无力患者T淋巴细胞亚型的影响

目的：观察胸腺切除(Tx)术对重症肌无力(MG)病人的临床疗效及对T淋巴细胞亚型的影响。方法：用许氏评分法观察30例伴胸腺增生或胸腺瘤的MG患者的病情严重程度及Tx术后2个月的临床疗效;采用直接免疫荧光染色和流式细胞仪技术测定60名志愿健康者和30例伴胸腺增生或胸腺瘤的MG患者Tx术前及术后2个月T淋巴细胞亚型的变化。结果：伴胸腺增生或胸腺瘤的MG病人Tx术前外周血中CD4＋T淋巴细胞的百分率较正常人显著增多(P＜0．01),CD8＋T淋巴细胞的百分率较正常人显著减少(P＜0．01),CD4＋/CD8＋T细胞的比例明显增高(P＜0．01)。伴胸腺增生MG病人Tx术后随着临床症状的改善,CD8＋T淋巴细胞的百分率较术前显著升高(P＜0．05),CD4＋/CD8＋T细胞的比例较术前显著下降(P＜0．05)。伴胸腺瘤MG病人Tx术后随着临床症状的改善,CD4+T淋巴细胞的百分率较术前显著下降(P＜0．05),CD4＋/CD8＋T细胞的比例较术前显著下降(P＜0．05)。结论：重症肌无力患者T淋巴细胞亚型的测定既可以为MG免疫病理学的发病机理的研究提供实验依据,也能为Tx治疗MG提供一个客观的实验室指标,为判断疾病的转归提供实验依据。     

重症肌无力患者末梢血Th1和Th2细胞内细胞因子的变化及意义

目的研究重症肌无力(MG)患者末梢血细胞因子及抗乙酰胆碱受体抗体(AchRab)水平,探讨细胞因子在MG发病中的作用。方法研究对象为17例MG患者,分为急性期组10例,非急性期组7例,设健康对照组15例。应用流式细胞术(FCM)测定末梢血产生各型细胞因子(CK)的CD4+T细胞%,采用酶联免疫吸附法(ELISA)测定血清中抗乙酰胆碱受体抗体(AchRab)。结果⑴MG患者急性期组和非急性期组IFN-γ+IL-4-CD4+T细胞%及AchRab的含量比健康对照组显著增多(P<0.05和P<0.001);⑵急性期组和非急性期组IFN-γ-IL-4+和IL-13+CD4+T细胞%比健康对照组显著减少(P<0.05);⑶IL-10+CD4+T细胞%各组之间无显著性差异;⑷各组IFN-γ+IL-4-CD4+T细胞%与AchRab均呈正相关。结论MG患者Th1和Th2细胞因子的平衡紊乱,Th1细胞因子IFN-γ对MG患者自身抗体的产生有促进作用。     

The early involvement of the innate immunity in the pathogenesis of late-onset Alzheimer's disease: neuropathological, epidemiological and genetic evidence

The idea that an inflammatory process is involved in Alzheimer's disease (AD) was proposed already hundred years ago but only the past twenty years inflammation-related proteins have been identified within plaques. A number of acute-phase proteins colocalize with the extracellular amyloid fibrils, the so called Aβ-associated proteins. Activated microglia and astrocytes surrounding amyloid deposits express receptors of innate immunity and secrete pro-inflammatory cytokines. In this paper we review the evidence for involvement of innate immunity in the early stages of the pathological cascade of AD. Diffuse plaques, the initial neuropathological lesion in the cerebral neocortex, contain next to Aβ also apolipoprotein E, clusterin, α1-antichymotrypsin and activated complement proteins. Interestingly, genetic studies have shown gene-loci to be associated with AD for all these proteins, except α1-antichymotrpsin. Fibrillar Aβ can, through stimulation of toll-like receptors and CD-14 on glial cells, activate pathways for increased production of pro-inflammatory cytokines. This pathway, inducing production of proinflammatory cytokines, is under genetic control. The finding that the responsiveness of the innate immunity is higher in offspring with a parental history of late-onset AD indicates heritable traits for AD that are related to inflammatory processes. Prospective epidemiological studies which report that higher serum levels of certain acute-phase proteins are associated with cognitive decline or dementia provide additional evidence for the early involvement of inflammation in AD pathogenesis. The reviewed neuropathological, epidemiological and genetic findings show evidence for involvement of the innate-immunity in the early stages of pathological cascade as well as for the hypothesis that the innate immunity contributes to the etiology of late-onset AD.     

Autoantigen-induced IL-13 mRNA expression is increased in blood mononuclear cells in myasthenia gravis and multiple sclerosis

Evidence has been presented for the involvement of immune mechanisms in the pathogenesis of myasthenia gravis (MG) and multiple sclerosis (MS). The production of autoantibodies in both diseases is regulated by T-cells by means of cytokines. Interleukin-13 (IL-13) is mainly produced by T-helper type 2 cells and induces B-cell proliferation and antibody class switch. The role of IL-13 in MG and MS is not known. We employed in situ hybridization with synthetic radiolabelled oligonucleotide probes to detect and enumerate blood and cerebrospinal fluid (CSF) mononuclear cells (MNC) expressing IL-13 mRNA from patients with MG, MS, optic neuritis (ON), other inflammatory neurological diseases (OIND) and healthy controls. MG is associated with elevated levels of acetylcholine receptor (AChR) reactive IL-13 mRNA expressing blood MNC compared to control patients. In MS, numbers of MBP-reactive IL-13 mRNA expressing MNC were higher compared to cultures without antigen stimulation. The levels of MBP-reactive IL-13 mRNA positive MNC were higher in MS compared to MG, but not other controls. There were no differences in spontaneous IL-13 mRNA expressing blood MNC numbers between MG, MS, ON and control patients. The data suggest the involvement of IL-13 in both MG and MS.     

Cytokines and the pathogenesis of myasthenia gravis

Myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG) are caused by autoantibodies against nicotinic acetylcholine receptor (AChR) in skeletal muscle. The production of anti-AChR antibodies is mediated by cytokines produced by CD4⁺ and CD8⁺ T helper (Th) cells. Emerging investigations of the roles of cytokines in MG and EAMG have revealed that the Th2 cell related cytokine interleukin 4 (IL-4), an efficient growth promoter for B-cell proliferation and differentiation, is important for anti-AChR antibody production. IL-6 and IL-10 have similar effects. The Th1 cytokine IFN-γ is important in inducing B-cell maturation and in helping anti-AChR antibody production and, thereby, for induction of clinical signs and symptoms. Results from studies of time kinetics of cytokines imply that IFN-γ is more agile at the onset of EAMG, probably being one of the initiating factors in the induction of the disease, and IL-4 may be mainly responsible for disease progression and persistance. Even though other Th1 cytokines like IL-2, tumor necrosis factor α (TNF-α), and TNF-β as well as the cytolytic compound perforin do not directly play a role in T-cell-mediated help for anti-AChR antibody production, they are actually involved in the development of both EAMG and MG, probably by acting in concert with other cytokines within the cytokine network. In contrast, transforming growth factor β (TGF-β) exerts immunosuppressive effects which include the down-regulation of both Th1 and Th2 cytokines in MG as well as EAMG. Suppressive effects are also exerted by interferon α (IFN-α). Based on elucidation of the role of cytokines in EAMG and MG, treatments that up-modulate TGF-β or IFN-α and/or suppress cytokines that help B-cell proliferation could be useful to improve the clinical outcome. © 1997 John Wiley & Sons, Inc. Muscle Nerve, 20, 543–551, 1997     

重症肌无力患者外周血microRNA-146a、炎症细胞因子的表达水平变化及其相关性分析

目的 探讨重症肌无力患者外周血microRNA-146a、炎症细胞因子（IL-6、CRP、TNF-α）的表达水平变化及相关性分析。 方法 选取2015年7月-2018年11月本院收治的重症肌无力患者58例作为试验组（MG组）,另选取同期体检健康者30例作为对照组;采集空腹外周静脉血,分离单个核细胞并提取总RNA;采用RT-PCR技术检测2组外周血单个核细胞总microRNA-146a的相对表达水平;采用ELISA技术检测2组外周炎症细胞因子（IL-6、CRP、TNF-α）的表达水平;比较2组microRNA-146a、炎症细胞因子（IL-6、CRP、TNF-α）的表达水平,分析重症肌无力患者microRNA-146a、症细胞因子（IL-6、CRP、TNF-α）表达水平与重症肌无力定量评分（QMGS）的相关性以及microRNA-146与三种炎症细胞因子表达水平的相关性。 结果 MG患者外周血microRNA-146a、IL-6、CRP、TNF-α高表达(P<0.05);MG患者外周血microRNA-146a、IL-6、CRP、TNF-α表达水平与QMGS评分呈正相关(r=0.795,0.642,0.365,0.743,P均<0.05);MG患者microRNA-146a表达水平与IL-6、TNF-α表达水平呈正相关(r=0.700,0.870,P<0.05),与CRP表达水平无相关性(r=0.235,P>0.05)。 结论 MG患者外周血存在microRNA-146a的高表达,且可能通过调控IL-6、TNF-α的表达来参与MG发病。