重症肌无力AChRAb与培养神经元nAChR免疫结合反应研究

目的 从离体细胞水平对重症肌无力（MG）患者伴有中枢神经系统（CNS0受损的机制进行探讨。方法 从MG患者和正常人血中提取IgG。体外培养新生SD大鼠皮层，脑干、海马神经元，同时培养TE-671细胞株作阳性对照，然后其与神经元特异性抗体及胆碱能神经元特异性抗体进行间接免疫荧光双标记，观察其免疫结合反应。结果 MG患者IgG可与离体培养的皮层，脑干、海马神经元及TE671免疫结合，而正常人血中提取的IgG则否。结论 MG患者外周IgG(AChRAb)可与离体培养的神经-烟碱型乙酰胆碱受体（nAChR)结合。是MG患者CNS受损的可能机制。     

重症肌无力中枢神经系统损害

从重症肌无力(MG)脑脊液AChRab的检出,脑电图异常、睡眠周期紊乱、诱发电位异常及认知功能障碍等方面来阐述其中枢神经系统损害。     

重症肌无力患者烟碱型乙酰胆碱受体抗体致鼠脑干听觉诱发电位

目的神经肌接头（NMJ）处乙酰胆碱（ACh）传递障碍，是重症肌无力（MG）发病机制。然而，近年有研究表明部分MG患者有中枢神经系统（CNS）受损的症状和神经电生理方面的异常表现，本研究为探讨其机制。方法从烟碱型乙酰胆碱受体抗体（nAChR－ab）阳性的全身型MG患者血清中提取IgG，将其注入SD大鼠脑室系统，观察其对脑干听觉诱发电位（BAEP）的影响。结果nAChR－ah使脑干听觉传导功能异常，表现为Ⅰ波后各波消失，Ⅰ－Ⅲ、Ⅰ－ⅤIPLs延长，Ⅴ／Ⅰ波幅比值降低。表明MG患者nAChR－ab可能与CNS中的神经－烟碱型乙酰胆碱受体（神经－nAChR）结合，BAEP异常可能与nAChR－ab结合听觉通路中继核团有关。结论nAChR－ah的病理作用不仅只限于NMJ处的nAChR，还可波及到脑干处的nAChR。     

用AChR单克隆抗体建立大鼠重症肌无力被动转移模型的研究

目的利用乙酰胆碱受体(AChR)单克隆抗体建立重症肌无力(MG)被动转移模型。方法将AChR单克隆抗体mAb35注入3种品系大鼠腹腔，观察其临床症状并行药理学和电生理学及超微结构鉴定。结果被动转移mAb35后3种大鼠均可出现肌无力症状。其临床症状、药理学特点、电生理特点和超微结构变化均与MG患者相似。结论利用AChR单克隆抗体可在此3种品系大鼠成功建立获得性自身免疫性MG模型。     

Titin抗体与重症肌无力

重症肌无力(Myasthenia Gravis,MG)是以神经肌肉接头处突触后膜烟碱型乙酰胆碱受体(AchR)损害为主的自身免疫性疾病,临床上约有85%~90%的患者体内能检测到乙酰胆碱受体抗体(AchR-Ab),但其浓度水平与发病严重程度无明显相关性,这可能是由于AchR-Ab对特异性抗原决定簇的异质性,也提示体内有其他抗体的存在,而这些抗体则主要针对肌细胞中具有重要功能的分子或抗原。近年来,部分MG患者血清中发现了骨骼肌柠檬酸提取物(CAE)抗体、肌连蛋白(Titin)抗体、肌内特异性激酶(MuSK)抗体、Ryan-odine受体(RyR)抗体等,且均与MG的发病机制有关,…     

重症肌无力免疫疗法新进展

重症肌无力(MG)是以乙酰胆碱受体抗体(AchRab)为主要致病因素的自身免疫性疾病,其治疗方法很多,但都以免疫疗法降低AchRab 为主。本文就免疫抑制剂、血液疗法、手术疗法和放射治疗等方面的新进展进行介绍。     

小儿重症肌无力的免疫调节治疗

用肾上腺皮质激素，人血球蛋白、胸腺肽三者联合的免疫调节治疗方案治疗重症肌无力患者６８例，并观察了乙酰胆碱受体抗体及免疫球蛋白在治疗前后的变化，结果提示重症肌无力患儿体内免疫调节紊乱，本免疫调节疗法疗效满意，简便经济，且达到免疫调节目的。     

眼肌型重症肌无力研究进展

重症肌无力（MG）是一种由乙酰胆碱受体（AChR）抗体介导，细胞免疫依赖，补体系统参与，主要累及神经肌肉接头突触后膜AChR的自身免疫性疾病。其中眼肌型重症肌无力（oMG）特指肌无力症状仅局限于眼外肌，而全身型重症肌无力（gMG）则是指除眼外肌外，无力症状还累及骨骼肌系统。oMG的自然病程复杂多变，临床表现时轻时重，且其中很大一部分患者在2年内还有可能逐渐发展成为gMG。     

乙酰胆碱受体抗体测定对儿童重症肌无力的诊断价值

重症肌无力(MG)是累及神经肌肉接头突触后膜乙酰胆碱受体的自身免疫性疾病,免疫学研究已发现,患者血清中针对靶细胞的抗乙酰胆碱受体抗体(AchRsb)滴度增加,并认为AchRab是MG的主要致病因子。故检测患儿血清AchRab具有诊断MG的特异性价值。本文应用ELASA法对63例MG患儿进行了血清AchRab测定,发现大多数患儿抗体滴度明显升高,能反映临床情况,具有很高的实验诊断价值。     

重症肌无力诊治进展

重症肌无力(myastheniagravis,MG)是一种神经肌肉接头传递障碍疾病,以骨骼肌无力、晨轻暮重、症状有波动为主要临床特点,主要由乙酰胆碱受体抗体(acetylcholinereceptorsantibody,AChR-Ab)等自身抗体介导、细胞免疫辅助、补体参与的自身免疫性疾病。Deenen等[1]通过对1990—2014年进行的24项研究进行分析显示,MG年发病率(3~28)/100万,患病率为(54~350)/100万。除AChR-Ab外,近年还发现一些新的抗体如抗肌肉特异性酪氨酸激酶抗体(musclespecifickinaseantibody,MuSK-Ab)、抗低密度脂蛋白受体相关蛋白4抗体(lipoproteinreceptor-relatedprotein4antibody,LRP4-Ab)也参与了部分MG的致病过程[2-4]。     

Acetylcholine receptor antibody in myasthenia gravis

Radioimmunoassay techniques were used to detect antibodies to the acetylcholine receptor (AAChR) in 164 patients with adult-onset myasthenia gravis. AAChR levels above 0.6 nM/l were considered pathological and were found in 67% of the patients with an average value of 58.99 +/- 125.02 nM/l (0.6-900.0). Correlation, with clinical functional status, the histopathological thymus alterations and the different therapeutics used did not disclose any statistically significant differences.     

重症肌无力血清乙酰胆碱受体抗体的阳性率及其影响因素

采用ABC-ELISA法检测162例重症肌无力患者的224份血清标本,100例正常人和78例其他疾病病人的血清中AchRab。重症肌无力病人的抗体阳性率为80.2％,其中单纯眼肌型63.1％,脊髓肌型90.0％,延髓肌型93.8％和全身肌型91.5％。合并胸腺瘤的阳性率为83.3％,与全组阳性率无显著性差异。激素和血浆交换治疗均未影响抗体阳性结果。随访观察表明,重症肌无力病人的AchRab阳性率与疾病严重程度不成线性相关。我们认为,AchRab滴度虽然与临床状况不相关,但在重症肌无力的诊断和自身免疫病因的研究中,仍是一项重要参数。     

重症肌无力患者外周血单个核细胞白细胞介素6活性变化

探讨白细胞介素 6(IL -6)在重症肌无力 (MG)发病机理中的作用及其临床意义。　　方法　采用3H -TdR掺入法检测 40例正常对照及 42例MG患者外周血单个核细胞IL -6分泌活性。　　结果　MG患者组IL -6活性显著高于正常对照组 ,且IL -6活性变化与乙酰胆碱受体抗体产生以及与MG临床类型、病情、预后密切相关。　　结论　IL -6在MG发病机理中起着重要作用 ,检测IL -6活性对区分MG临床类型、判断病情、推测预后、指导治疗有重要的参考价值。     

重症肌无力患者血清IgG-乙酰胆硷受体抗体亚型研究

目的 探讨重症肌无力（ＭＧ）患者血清ＩｇＧ－乙酰胆硷受体抗体（ＡＣｈＲＡｂ）亚型的分布规律及其临床意义。方法 采用ＡＢＣ－ＥＬＩＳＡ法检测４３例ＭＧ组和２５例临床对照组、２０例正常对照组血清中ＩｇＧ－ＡＣｈＲＡｂ亚型ＩｇＧ１－４。结果 ＭＧ组与两对照组相比ＩｇＧ１和ＩｇＧ４亚型抗体无显著差别,ＩｇＧ２亚型抗体显著升高（Ｐ〈０．０５）,ＩｇＧ３亚型抗体显著降低（Ｐ〈０．０５）;ＭＧ组各临床类型间各亚型抗体无显著差别。结论 ＩｇＧ－ＡＣｈＲＡｂ亚型以ＩｇＧ２活性为主,但未显示与ＭＧ临床类型有关。     

重症肌无力病人乙酰胆碱受体抗体的测定及临床意义

用ＥＬＩＳＡ（固相酶联免疫吸附）法测定１７２例ＭＧ病人血清乙酰胆碱受体抗体（ＡｃｈＲａｂ），结果显著高于健康献血员组和非ＭＧ病人组。不同性别、病程及临床类型与ＡｃｈＲａｂ无相关性，但４１～５０岁组的显著高于其他年龄组。６７例类固醇激素治疗组、２２例大剂量两种球蛋白治疗组、１２例胸腺切除术组及３例ＭＧ危象病人２４次血浆交换疗法（ＰＥ）组，治疗后伴随肌无力症状的好转，ＡｃｈＲａｂ均显著低于治疗前。结果表明：ＡｃｈＲａｂ测定为ＭＧ诊断提供了可靠的实验依据，为类固醇激素、大剂量丙种球蛋白、胸腺切除术和ＰＥ等治疗ＭＧ提供理论依据和疗效评定的实验指标，进一步证实了ＭＧ免疫学发病机理。     

重症肌无力患者血清白细胞介素—6水平测定

目的探讨重症肌无力(MG)与白细胞介素-6(IL-6)的关系.方法采用双抗体夹心ELISA法对30例MG患者用糖皮质激素(GC)治疗前、治疗2个月后和22例正常对照血清IL-6、乙酰胆碱受体抗体(AchRab)水平进行检测.结果MG患者组血清IL-6水平显著高于对照组(P＜0.01),MG患者组血清IL-6水平在用GC治疗2个月后显著降低(P＜0.01),其血清IL-6与血清AchRab水平呈正相关(r=0.693,P＜0.01).结论IL-6与MG发病密切相关,IL-6参加了MG的免疫病理过程;检测血清IL-6水平对MG临床有重要价值;GC可抑制IL-6合成及AchRab产生.     

Neonatal myasthenia gravis: Clinical and immunological study of seven mothers and their newborn infants

We studied 7 mothers with myasthenia gravis (MG) and their infants. We confirmed that the development of neonatal MG was not related to the serum titer of maternal anti-acetylcholine receptor antibody (anti-AChR ab). To investigate the possibility that specific immunization of the newborn infant had occurred, serial serum determinations of total and 'specific' anti-AChR IgG and IgM were performed. We found that: the decay in total IgG was within the normal range in all the babies; there was a shorter half-life of 'specific' IgG, compared to total IgG, in 3 of the cases, 2 of which did have neonatal MG; no difference was found between the decay of anti-AChR ab in the babies who had neonatal MG and those who did not; there was no anti-AChR IgM-associated activity. Our data suggest that neonatal MG is due to maternal anti-AChR abs and that affected infants do not produce specific antibodies.     

Clinical findings in MuSK‐antibody positive myasthenia gravis: A U.S. experience

We performed a retrospective chart review on 53 muscle‐specific kinase antibody (MuSK‐Ab)‐positive myasthenia gravis (MG) patients at nine university‐based centers in the U.S. Of these, 66% were Caucasian, 85% were women, and age of onset was 9–79 years. Twenty‐seven patients were nonresponsive to anticholinesterase therapy. Myasthenia Gravis Foundation of America improvement status was achieved in 53% patients on corticosteroids, 51% with plasma exchange, and in 20% on intravenous immunoglobulin (IVIG). Thymectomy was beneficial in 7/18 patients at 3 years. Long‐term (≥3 years) outcome was very favorable in 58% of patients who achieved remission and/or minimal manifestation status. Overall, 73% improved. There was one MG‐related death. This survey reinforces several cardinal features of MuSK‐Ab‐positive MG, including prominent bulbar involvement and anticholinesterase nonresponsiveness. Facial or tongue atrophy was rare. Most patients respond favorably to immunotherapy. The best clinical response was to corticosteroids and plasma exchange, and the poorest response was to IVIG. Long‐term outcome is favorable in about 60% of cases. Muscle Nerve, 2009     

Widely varying TNF-α levels in patients with myasthenia gravis

Animal studies have indicated an important role of tumor necrosis factor-alpha (TNF-α) in the pathogenesis of myasthenia gravis (MG), and trials of monoclonal antibodies that block TNF-α have shown clinical improvement. However, before a TNF-α blocking agent is proposed for treatment of MG, whether serum TNF-α level correlates with the patient’s condition should be confirmed. Therefore, we evaluated the relationship between the serum TNF-α level and clinical factors, including the quantitative MG score and the anti-acetylcholine receptor antibody level, in 33 MG patients. TNF-α levels ranged from 0.44 to 3.63 pg/mL and did not correlate with clinical factors. Overall, we found that serum TNF-α levels varied greatly among MG patients.