难治性重症肌无力的治疗管理

重症肌无力是一种影响突触后膜的自身免疫性疾病,病态疲劳性肌无力为主要特点.近年来较多研究显示多种免疫抑制剂和单克隆抗体对重症肌无力的治疗具有重要作用.进一步熟知难治性重症肌无力的治疗进展对于改善患者的临床症状具有深远意义.     

肌无力危象的治疗研究进展

重症肌无力是发生在神经肌肉接头处、由抗体介导、细胞免疫依赖、补体参与的自身免疫性疾病,死亡率较高。肌无力危象的急救处理包括胆碱酯酶抑制剂、糖皮质激素、免疫抑制剂、静脉注射人免疫球蛋白、血浆置换、胸腺切除、机械通气等。近年来,随着国内外医疗水平的提高及免疫学研究的不断进展,对肌无力危象的治疗有了更深入的认识,其病死率呈逐渐下降趋势,使该病治愈成为可能。本文就近些年来对肌无力危象的治疗进行综述,为临床治疗提供参考。     

中西医结合治疗对重症肌无力患者外周血Treg、Tfh细胞的影响

目的 探索中西医结合治疗对重症肌无力患者外周血Treg、Tfh细胞的影响.方法 选取我院长期随访治疗的重症肌无力(MG)患者及根据年龄、性别匹配的健康对照,比较患者与健康对照组外周血Tfh、Treg细胞及Tfh/Treg比值,监测治疗前后重症肌无力患者外周血上述指标的变化.结果 健康对照组,眼肌型、全身型重症肌无力患者外周血Treg细胞以及重症肌无力患者治疗前后差异无统计学意义(P>0.05).治疗前重症肌无力患者Tfh及Tfh/Treg比值高于健康对照组(P<0.01),全身型重症肌无力外周血Tfh显著高于眼肌型(P<0.01),治疗后全身型重症肌无力患者外周血Tfh较治疗前下降.重症肌无力患者治疗前后Tfh/Treg差异无统计学意义(P>0.05).结论 重症肌无力患者外周血免疫功能特别是外周血Tfh存在异常,中西医结合综合治疗可改善这种免疫功能异常,达到治疗作用.     

肾移植受者重症肺部感染救治期间免疫抑制剂的调整

目的 探讨重症肺部感染肾移植受者救治期间移植肾功能的保护.方法 对15例肺部感染的肾移植患者的临床资料进行回顾性分析.结果 15例重症肺部感染中有11例治愈,移植肾功能正常;死亡2例,放弃治疗2例.有12例检出病原菌,其中混合感染10例.结论 重症肺部感染是肾移植术后的主要并发症,死亡率极高,早期诊断、及时调整免疫抑制剂方案以保护移植肾的功能和尽早确定病原菌等均有利于提高其抢救成功率.     

长期硫唑嘌呤治疗可消除重症肌无力病人胸腺的淋巴滤泡增生

重症肌无力病人的胸腺是最初发生自身免疫的器官,尤其是病程短的年轻病人,胸腺切除往往完全缓解,不需免疫抑制治疗。65～80％病人的胸腺炎伴有血管周围间隙和胸腺髓质淋巴滤泡增生(LFH),但一般不累及胸腺皮质。长期应用免疫抑制剂治疗重症肌无力应首选硫唑嘌呤(AZA)。Mertens等认为,长期应用AZA治疗有效,肌无力症状为明显改善,也不需切除胸腺,而用可的松则引起胸腺可逆性萎缩,但AZA是否影响胸腺形态学变化还不清楚。作者再次检查16例重症肌无力病人的非肿瘤性胸腺的标本。这些病例都是先用免疫     

一例重症肌无力危象病人的心理疏导

重症肌无力是累及神经肌肉接头突触后膜上乙酰胆碱受体的自身免疫性疾病。临床特征为部分或全身横纹肌异常地容易疲劳。胸腺瘤合并重症肌无力治疗较为棘手,术后并发肌无力危象给治疗带来了更大的困难,我科于1999年8月收治一例重症肌无力病人,术后当日即发生肌无力危象,入ICU进行呼吸机辅助呼吸近一个月,对呼吸机产生依赖心理,现将临床对其进行心理疏导措施介绍如下。     

重症肌无力治疗进展

目前,虽有许多治疗重症肌无力(MG)的方法,如胆碱酯酶抑制剂、类固醇激素(如强的松龙)、免疫抑制剂(如硫唑嘌呤,环磷酰胺)、血浆去除法、胸腺切除和免疫调节剂等,但多数药物治疗疗效不够满意。胸腺切除是国外治疗MG的常用手段之一,疗效肯定,复发率小。目前血浆去除等其他治疗MG的新方法也相继用于临床,疗效较好,值得推广应用。现就胸腺切除治疗重症肌无力及其他治疗新进展综述如下。     

中西医结合治疗重症肌无力对Treg/Th17免疫细胞及相关细胞因子的影响

目的 比较中西医结合治疗(包括免疫抑制剂和以补中益气汤为主的辩证加减联合治疗)和单纯免疫抑制剂治疗重症肌无力两种治疗方案对Treg/Th17免疫细胞及相关细胞因子的影响.方法 选择2017年1月至2018年12月收治的重症肌无力患者80例,随机分为两组(I组和II组)进行临床治疗,其中I组(42例)采用免疫抑制剂(甲泼尼松龙和硫唑嘌呤)配伍中药重剂补中益气汤联合治疗;II组(38例)采用单纯免疫抑制剂(甲泼尼松龙冲击配伍硫唑嘌呤)治疗.监测两组患者治疗12个月前后的Treg/Th17细胞及相关细胞因子IL-6、IL-17、IL-21的变化,同时观察MG特异性抗体乙酰胆碱受体抗体(AChRAb)水平变化及MG临床绝对评分标准来判定治疗后12个月前后的临床疗效.结果(1)两组治疗后Treg和Th17细胞均较治疗前差异有统计学意义(P<0.001),I组较II组Treg和Th17细胞变化更显著(P<0.001).(2)治疗后两组MG患者细胞因子IL-6、IL-17和IL-21水平均显著降低(P<0.001),且I组明显低于II组(P<0.001).(3)两组MG患者治疗前AChRAb水平差异无统计学意义(P>0.05),治疗后两组均显著降低(P<0.01);而I组较Ⅱ组表现出疗效差异明显,患者血清AChRAb水平降低更明显(P<0.001).(4)两组患者MG绝对评分治疗前组间及II组治疗前后比较差异均无统计学意义(P>0.05);治疗后两组组间MG绝对评分及I组治疗前后比较差异均有统计学意义(P<0.05).结论 中西医结合治疗重症肌无力可使Treg和Th17细胞变化更显著、细胞因子IL-6、IL-17和IL-21表达水平降低更明显、乙酰胆碱受体抗体(AChRAb)降低更明显、临床绝对评分明显降低,患者的临床症状缓解率高,长效性和稳定性好.     

带血管蒂胎胸腺移植治疗重症肌无力的临床护理

重症肌无力是累及神经肌肉接头处突触后膜上乙酰胆碱受体的自身免疫性疾病,临床特征为部分或全身横纹肌异常地容易疲劳。胸腺瘤合并重症肌无力(MG)治疗较为棘手,是否手术治疗仍有争论,除肿瘤本身具有浸润性外,MG自身免疫变化加重了治疗的复杂性。我科于1998年11月至2000年4月应用胸腺切除并带血管蒂胎胸腺移植治疗MG 5例,取得良好效果。现将临床护理介绍如下。     

重症肌无力的免疫学研究进展

重症肌无力是抗乙酰胆碱受体抗体介导的、细胞免疫依赖性、补体参与的神经肌肉接头处的自身免疫病,其发病本质就是针对乙酰胆碱受体的免疫应答异常.辅助性T细胞、细胞因子及胸腺在重症肌无力的发病机制中起重要作用,肌细胞亦主动地参与了重症肌无力的发病过程.重症肌无力的免疫启动目前多倾向于交叉反应学说.     

Myasthenia Gravis

The autoimmune pathogenesis of myasthenia gravis is relatively well understood. The current options for treatment of this disease are acute and long term immunotherapies, acetylcholinesterase inhibitors and thymectomy. Many factors influence the timing of initiation of immunomodulatory therapy in myasthenia gravis and both disease factors, such as stage and severity, and patient factors, such as age, pregnancy and intercurrent illness, must be considered. Decisions regarding the choice of therapy can be difficult because of the limited number of randomised controlled trials that have been performed in myasthenic patients. In general, acetylcholinesterase inhibitors alone are used only in mild ocular disease, and in the majority of other patients immunomodulatory therapy is begun early. Corticosteroids are the most commonly used initial therapy, followed by azathioprine. In refractory cases, the available options include immunosuppressants such as cyclosporin, mycophenolate mofetil and cyclophosphamide. Plasmapheresis and intravenous immunoglobulin are important in the treatment of acute exacerbations and myasthenic crisis and in the perioperative setting. Despite many years of experience, the role of thymectomy in improving long term outcome in nonthymomatous myasthenia gravis remains controversial.     

Antibodies Against Nicotinic Acetylcholine Receptor and Skeletal Muscle in Human and Experimental Myasthenia Gravis

Using rocket immunoelectrophoresis and indirect haemagglutination tests, antibodies to nicotinic acetylcholine receptor (n-AChR) from Torpedo marmorata were detected in sera from rabbits with experimental myasthenia but not in sera from patients with myasthenia gravis or in rabbit antisera to a partly purified skeletal muscle antigen. Antibodies to this antigen were demonstrated in sera from patients with myasthenia gravis but not in sera from rabbits with experimental myasthenia. The results indicate that there is no immunological cross-reaction between the muscle antigen and n-AChR from Torpedo marmorata, and little or no cross-reactivity between these n-AChR antibodies and possible muscle n-AChR antibodies in myasthenia gravis patients.     

Myasthenia gravis: familial occurrence. A study of 1100 myasthenia gravis patients

Eleven-hundred myasthenia gravis cases observed by the author in a period of 37 years are reviewed. The ratio of familial incidence was 4.23%. Transitory (neonatal) myasthenia in new-born babies should be separated from the familial cases. In familial myasthenia gravis both maternal and paternal line can occur. The majority of the cases are similar to the generalized, acquired myasthenia gravis, still there are some myasthenic familial congenital patients, too. Some rare instances are reported, among them a unique family with six sisters suffering from myasthenia gravis. Genetic line and HLA antigens' role are dealt with. Observation of familial myasthenia cases may contribute to the knowledge of the immunologic and clinicopathologic background of the disease.     

Antibodies Against Nicotinic Acetylcholine Receptor and Skeletal Muscle in Human and Experimental Myasthenia Gravis

Using rocket immunoelectrophoresis and indirect haemagglutination tests, antibodies to nicotinic acetylcholine receptor (n-AChR) from Torpedo marmorata were detected in sera from rabbits with experimental myasthenia but not in sera from patients with myasthenia gravis or in rabbit antisera to a partly purified skeletal muscle antigen. Antibodies to this muscle antigen were demonstrated in sera from patients with myasthenia gravis but not in sera from rabbits with experimental myasthenia. The results indicate that there is no immunological cross-reaction between the muscle antigen and n-AChR from Torpedo marmorata , and little or no cross-reactivity between these n-AChR antibodies and possible muscle n-AChR antibodies in myasthenia gravis patients.     

重症肌无力患者抗Ryanodine受体抗体检测及其意义

本实验应用Westernblot分析 4 4例伴不同胸腺病理类型重症肌无力 (MG )患者血清中Ryanodine受体 (RyR )抗体特异性 ,同时应用ELISA法检测 1 6 9例伴不同胸腺病理类型MG血清中RyR抗体水平。结果显示在Westernblot法分析中 ,2 4例伴胸腺瘤重症肌无力 (MGT )患者血清中有 1 9例可见到RyR抗体阳性条带 ,2 0例非胸腺瘤重症肌无力 (NTMG )患者血清中仅1例可见RyR抗体阳性条带 ,2 5例非MG个体 (NMG )均未见RyR抗体阳性条带。MGT患者血清中RyR抗体阳性条带检出率明显高于NTMG和NMG组 (P <0 0 1 )。在ELISA法检测中 ,MGT组患者血清中RyR抗体水平明显高于NTMG组、其他神经系统疾病 (OND )组、正常对照 (NC )组 (P <0 0 1 ) ;5 9例MGT患者血清中 4 6例RyR抗体阳性 ,2 83例NTMG、OND、NC组检测血清中 1 9例RyR抗体阳性 ,ELISA法检测MGT患者血清中RyR抗体敏感性为 78% ,特异性为 93 3%。结果表明RyR抗体检测是诊断MGT特异性较高的实验室指标 ,具有重要的临床意义     

Clinicopathological study of thymomas--correlation of histologic subtype to myasthenia gravis and prognosis

Thymoma is the most common primary tumor of anterior superior mediastinum. Sixty cases of thymomas over a 12 year period were analysed and the histologic subtype, according to Marino and Muller-Hermilink, classification was correlated with presence or absence of myasthenia gravis (MG) and capsular invasion. Thirty four patients had myasthenia gravis associated with thymoma and there was one case of pure red cell aplasia. There were 3 (1) predominantly cortical, 28 (20) cortical, 12 (9) mixed, 16 (4) medullary thymomas and 1 (0) thymic carcinoma (Figures in parenthesis indicate number of cases associated with MG). Capsular invasion was seen in 25 cases. Association with myasthenia gravis and capsular invasion were seen predominantly in cortical and mixed thymomas which were also associated with aggressive behaviour.     

The pathogenesis of myasthenia gravis — A hypothesis

We have suggested that a thymic factor plays a critical role in the pathogenesis of myasthenia gravis. The presence of specific ACh R antibodies in more than 90% of patients with myasthenia gravis has provided us with a marker for this disorder and has greatly increased our understanding of the pathophysiology. These antibodies can induce physiological parameters similar to those seen in myasthenia gravis following passive transfer to experimental animals and can accelerate degradation of ACh R in myotube culture. However, clinical studies suggest that additional factors of thymic origin are necessary for the development of the clinical features of myasthenia gravis. While the nature of the thymic factor(s) is speculative, this hypothesis has a significant clinical implication as it argues for an early, total thymectomy as the treatment of choice for myasthenia gravis.     

The immunopathology of myasthenia gravis.

Experimental autoimmune myasthenia gravis, induced by immunization with solubilized acetylcholine receptors, has proven an excellent animal model for the study of myasthenia gravis. The role of the thymus in myasthenia gravis is not yet known. Its content of skeletal muscle elements and acetylcholine receptors and the presence of germinal centers in myasthenia gravis suggest that the thymus could be a site of autoimmunization. An effector role has not been demonstrated for T cells in the pathogenesis of experimental autoimmune or clinical myasthenia gravis, but helper T cells participate in the rat's autoantibody response to acetylcholine receptors. Antibodies and lymphocytes reactive with acetylcholine receptors are demonstrable in the peripheral blood of patients with myasthenia gravis and appear to be specific for this disease. Parallel studies of both experimental autoimmune and clinical myasthenia gravis have provided evidence for an autoimmune basis for the pathophysiology in myasthenia gravis. Antiacetylcholine receptor antibodies appear to play a central role in impairing neuromuscular transmission. Numerous antibody specificities have been described, but none seems to be directed at the acetylcholine binding site of the receptor. Addition of antiacetylcholine receptor antibodies to cultured muscle cells, in the absence of complement, causes redistribution of the receptors on the membranes of myotubes, accelerated receptor degradation, apparent impairment of ionophore function, and loss of sensitivity to acetylcholine. In vivo complement appears to be an important mediator of antiacetylcholine receptor antibody pathogenicity. Its presence is essential for the passive transfer of experimental autoimmune myasthenia gravis with antibodies. In muscle biopsy specimens from patients with myasthenia gravis, IgG and C3 have been demonstrated on the postsynaptic membrane and on degenerated fragments of membrane in the synaptic cleft. This suggests that complement activation in vivo is associated with focal lysis of the postsynaptic membrane. A causal relationship appears to exist between the binding of antibody to acetylcholine receptors, the reduction in muscle acetylcholine receptors, and impairment of neuromuscular transmission.     

重症肌无力单核苷酸多态性的研究进展

重症肌无力（MG）是一种由神经-肌肉接头处传递功能障碍所引起的获得性自身免疫性疾病，其发病机制目前尚未完全明确。经相关研究表明，多因素多基因的积累共同导致了重症肌无力的发生，其中遗传因素占有重要作用。单核甘酸多态性（ SNP ）是人类基因组中最常见的多态性，在已经发现的多态性中有高达90％以上是以单核苷酸多态性的形式存在的。目前研究人员已经发现大量与重症肌无力密切相关的风险单核苷酸多态性，该文将对最近几年重症肌无力发病风险与单核苷酸多态性的相关性研究进行综述。