黄芪复方对重症肌无力患者血清乙酰胆碱受体抗体水平的影响

目的采用中药黄芪复方调节重症肌无力(myastheniagravis,MG)患者血清乙酰胆碱受体抗体(acetylcholinereceptorantibody,AChRAb)水平,以探讨其治疗MG的可能作用机制。方法应用酶联免疫吸附法(ELISA)检测74例MG患者治疗前后血清AChRAb水平,并采用许(氏)临床绝对和相对记分法观察病情严重程度和判定中药复方疗效。结果MG患者治疗前血清AChRAb水平(108±007)显著高于健康对照组(016±011)(P<001),治疗后MG患者血清AChRAb水平(072±006)明显下降(P<001)。结论具有补益脾肾作用的中药黄芪复方能下调MG患者血清AChRAb水平,从而纠正MG患者免疫失衡状态,临床绝对记分和相对记分对其疗效的判定有一定意义。     

RIA和ELISA检测血清乙酰胆碱受体抗体对重症肌无力诊断的准确性和一致性

目的 研究放射免疫沉淀法(radioimmunoprecipitation assay, RIA)和酶联免疫吸附法(enzyme linked immunosorbent assay, ELISA)测定乙酰胆碱受体抗体(anti-acetylcholine receptor antibody, AChR-Ab)对诊断重症肌无力(myasthenia gravis, MG)的敏感度和特异度,并对不同方法检测AChR-Ab的一致性进行检验。方法 本研究采用回顾性的方法,收集在北京协和医院神经科MG专科门诊诊断的未行免疫治疗的MG和非MG对照血清,应用RIA和ELISA检测AChR-Ab,对两种检测方法的敏感度和特异度进行验证,评估两种方法的相关性和一致性。结果 共募集120例MG,其中眼肌型54例,全身型66例;非MG对照102例,其中其他神经肌肉病43例,自身免疫病9例,健康体检者50名。MG诊断方面,RIA和ELISA的灵敏度分别为75.00%和71.67%,特异度分别为99.01%和96.08%,阳性预测值分别为98.9%和95.56%,阴性预测值分别为77.09%和74.24%。S...     

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。     

重症肌无力患者血清中抗心磷脂抗体测定的意义

目的 观察IgG-ACA与重症肌无力患者的关系。方法 应用酶联免疫吸附法,测定了94例重症肌无力(MG)患者和40例健康对照者血清中抗心磷脂抗体水平,(IgM-ACA和IgG-ACA)。结果 94例MG患者及40例健康对照者血清中IgM-ACA均为阴性;94例MG患者中30例IgG-ACA阳性(30/94,31.9％),40例健康对照者中仅2例阳性(2/40,5％),二者差异有非常显著性(P<0.01)。血清IgG-ACA水平与患者的年龄、性别、病型均无关(P>0.05),而与胸腺病理密切相关(P<0.01)。30例胸腺瘤患者中,14例阳性(14/30,46.7％),64例不伴胸腺瘤的MG患者中,16例阳性(16/64,25％),二者相比,差异有非常显著性(P<0.01)。IgG-ACA阳性患者中,1/3滴度较高(至少为正常值的2倍)。结论 通过对IgG—ACA的测定,不仅对MG是否合并胸腺瘤起初步筛选作用,而且是MG患者并发凝血机制方面异常的一个警惕性标志。     

重症肌无力发病的非乙酰胆碱受体抗体机制

重症肌无力 (ＭＧ)是一种主要由乙酰胆碱受体 (ＡＣｈＲ)抗体介导的自身免疫性疾病。然而 ,约有 1 5 %的ＭＧ患者血清中未检测到ＡＣｈＲ抗体 ,这些患者被称为抗体阴性重症肌无力 (ｓｅｒｏｎｅｇａｔｉｖｅＭＧ ,ＳＮＭＧ) [1 ] 。由于ＳＮＭＧ患者的临床表现与抗体阳性的ＭＧ患者基本相似 ,对免疫抑制剂治疗亦敏感 ,而且给小鼠注射ＳＮＭＧ患者的血清或ＩｇＧ亦能复制出ＭＧ模型[2 ] ,因此 ,对ＭＧ发病机制而言 ,除ＡＣｈＲ抗体的介导外 ,可能还有其他的抗体或分子参与。近年来对ＭＧ发病的非ＡＣｈＲ抗体机制研究取得了一系列的进展 ,综…     

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。     

肌无力综合征与抗乙酰胆碱酯酶抗体

肌无力综合征与抗乙酰胆碱酯酶抗体唐健袁锦楣郝洪军朱美财我们测定了５１例肌无力综合征患者血清中抗乙酰胆碱酯酶抗体（Ａｎｔｉ－ＡＣｈａｓｅＡｂ），并对其在肌无力发病中的可能机制进行了初步探讨。材料和方法：５１例肌无力患者作为实验组，其中男２６例，女２５例...     

重症肌无力患者血清中Ryanodine受体抗体检测及其临床意义

目的　探讨Ryanodine受体 (RyR)抗体在重症肌无力 (MG)诊断中的临床意义。方法　以差速离心法提取富含RyR的肌质网 (SR)提取物 ,建立ELISA RyR抗体检测系统 ,分析 6 6例伴胸腺瘤的MG(MGT)、98例非胸腺瘤MG(NTMG)和 5 0例非重症肌无力 (NMG)及 12 3名健康人 (NC)血清中RyR抗体水平。 结果　MGT组RyR抗体阳性检出率显著性高于NTMG组和NMG组 (P <0 0 1) ,敏感性和特异性分别达 81 8%和 94 5 %。不同胸腺组织学类型MGT之间RyR抗体阳性检出率差异无显著意义 (P >0 0 5 )。RyR抗体呈阳性MG组的年龄、临床评分和乙酰胆碱受体抗体水平均显著高于RyR抗体阴性MG组 (P <0 0 1)。RyR抗体水平同MG患者临床症状的严重程度呈正相关 ,尤其是MGT组 (r =0 6 2 6 ,P <0 0 1)。不同胸腺组织学类型MGT中以上皮细胞型相关性最高 (r =0 5 92 ,P <0 0 1)。结论　RyR抗体检测对诊断MGT具有较高的敏感性和特异性 ,并且与MG患者临床症状的严重程度呈正相关。     

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。     

Passive transfer of experimental autoimmune myasthenia gravis by monoclonal antibodies to the main immunogenic region of the acetylcholine receptor

Experimental autoimmune myasthenia gravis (EAMG) was passively transferred to rats by injecting monoclonal antibodies (mAbs) directed at the main immunogenic region (MIR) of the nicotinic acetylcholine receptor (AChR). The MIR is located on the extracellular part of the AChR alpha-subunit. All four mAbs directed at the MIR which were tested were very efficient in inducing EAMG: within 2 days the rats became moribund or very weak and their muscle AChR content decreased to about 50% of normal. These mAbs are of two different IgG subclasses (IgG1 and IgG2a) and derived from rats immunized with AChR from either fish electric organs or mammalian muscles. One mAb directed at the extracellular side of the beta-subunit did not cause AChR loss or induce symptoms of EAMG. mAbs to the cytoplasmic side were, as expected, ineffective.     

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.     

Cellular response to human acetylcholine receptor in patients with myasthenia gravis

A preparation of human skeletal muscle acetylcholine receptor (AchR) was used in vitro as an antigen to stimulate lymphocytes from patients with myasthenia gravis (MG). Clinical data obtained from the patients included duration and severity of disease; history of steroid treatment or prior thymectomy; and the presence of thymoma. Lymphocytes from patients with MG showed a significantly higher response to human AchR antigen than did lymphocytes from control subjects. Previous studies of cellular response to AchR have used receptor prepared from eel or ray electric organs. By stimulating lymphocytes from MG patients with a preparation of human AchR, we have come one step closer to documenting a possible contribution of a cellular immune response to the pathogenesis of MG.     

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.     

重症肌无力患者血清Titin抗体和AchR抗体检测的意义

目的 探讨重症肌无力(MG)患者血清Titin抗体及乙酰胆碱受体(AchR)抗体的检测意义.方法 采用酶联免疫吸附试验(ELISA)对81例MG患者和80例对照组成员进行Titin和AchR抗体的检测.结果 Titin抗体对MG具有特异性,它在合并胸腺瘤的MG(MGT)、晚发型MG患者中有较高的阳性率(分别为80%、69.4%)和抗体水平,明显高于早发型MG患者的阳性率(25%)和抗体水平,差异均有统计学意义(P<0.05).而早发型MG患者中AchR抗体阳性率比晚发型MG患者明显增高.并且早发型MG患者的AchR抗体水平也明显高于晚发型MG和MGT患者,差异均有统计学意义(P<0.05).结论 两种抗体检测为MG诊断和病因学研究提供了重要证据,联合检测可以提高MG诊断的灵敏度.     

Clonotypic analysis of the antibody response to the acetylcholine receptor in experimental autoimmune myasthenia gravis

Autoreactive B cells reactive with the acetylcholine receptor (AChR), and the antibodies produced by them, are proposed to play a primary role in the immunopathology of myasthenia gravis and its animal models. Therefore, the anti-AChR antibody response induced in rats was characterized for the clonotypic heterogeneity, isotype distribution, and affinity by isoelectric focusing (IEF) and affinity immunoblotting. It was determined that the rat anti-AChR serum antibody was relatively heterogeneous, reflecting the oligoclonality of the response. Furthermore, isotypic dominance by IgG2a was observed in that the majority of clonal products detected by IEF were of this isotype in both primary and secondary responses. Lastly, the clonotypic anti-AChR antibodies were of relatively low affinity (avidity) when compared to antibodies reactive with the highly immunogenic protein antigen, keyhole limpet hemocyanin; anti-AChR antibody avidity did not appear to increase when the antibodies in the secondary response were compared to antibodies in the primary response. These antibody characteristics are discussed in terms of their role in disease induction.     

糖皮质激素受体阻断对大鼠实验性自身免疫性重症肌无力的影响

研究重症肌无力（ＭＧ）患者外周血白细胞糖皮质激素受体（ＧＲ）减少，而血浆皮质醇则在正常范围，探讨其与ＭＧ发病的关系。方法ＳＤ大鼠３２只，随机分成４组。实验组先以ＧＲ的竞争性拮抗剂米非司酮（ＲＵ３８４８６，ＲＵ４８６）阻断其ＧＲ，再以从人肌肉中粗提的乙酰胆碱受体（ｎＡＣｈＲ）进行免疫；实验对照组单用ｎＡＣｈＲ，试剂对照组只用ＲＵ４８６，而正常对照组仅用福氏佐剂。以临床症状、血清抗ｎＡＣｈＲ抗体（ｎＡＣｈＲ－ａｂ），重复刺激坐骨神经递减幅度为观察指标。结果实验组的临床症状和ｎＡＣｈＲ－ａｂ滴度升高及肌电图递减幅度均较明显，经ｔ检验分析，均与实验对照组有显著性差异（Ｐ＜０．０５），而试剂对照组和正常对照组均无ＭＧ的表现。结论ＧＲ被阻断后，对大鼠的实验性自身免疫性ＭＧ（ＥＡＭＧ）发病有易化作用。     

Breakage of tolerance to hidden cytoplasmic epitopes of the acetylcholine receptor in experimental autoimmune myasthenia gravis

The acetylcholine receptor (AChR) is the major autoantigen in the antibody-mediated disease myasthenia gravis (MG) and its animal model experimental autoimmune myasthenia gravis (EAMG). This study demonstrates that rats immunized with a recombinant fragment corresponding to the normally exposed extracellular region of the rat AChR -subunit first develop antibodies to the injected extracellular portion only, but later develop antibodies to intracellular cytoplasmic epitopes of AChR. The presence of autoantibodies to intracellular epitopes seems to be correlated with development of clinical signs of disease. We propose that a similar process of epitope spreading may take place in the natural course of myasthenia.