眼肌型及全身型重症肌无力患者外周血T淋巴细胞Fas的表达

目的 探讨Fas介导的细胞凋亡与眼肌型(ocular myasthenia gravis,OMG)及全身型重症肌无力(generalized myasthenia gravis,GMG)发病的关系.方法 采用流式细胞技术检测4例OMG、13例GMG患者及13例健康对照组外周血淋巴细胞中CD4、CD8及Fas的表达.结果 OMG、GMG组与对照组外周血T淋巴细胞表面CD4、CD8分子表达的差异无统计学意义(P>0.05).GMG组与对照组外周血T淋巴细胞中Fas+细胞比例的差异有统计学意义(41.72%±8.73%、31.22%±13.00%,P:0.017).GMG组与对照组Fas表达增高者比例的差异有统计学意义(61.5%、15,4%,P=0.041).Fas表达增高的GMG患者病情较重.病程较长.胸腺瘤发生率较高.OMG与GMG组外周血T淋巴细胞中Fa8+、CD4+Fas+、CD8+Fas+细胞比例差异无统计学意义(P>0.05).结论 GMG患者外周血T淋巴细胞中Fas的表达升高,OMG与GMG患者外周血T淋巴细胞中Fas的表达无显著差异,二者可能同属一种系统性疾病.     

重症肌无力患者外周血CD+4 CDhigh25 T细胞及其动态观察

目的 研究重症肌无力(myasthenia gravis, MG)患者外周血CD+4 CDhigh25 T细胞的水平,以及各种治疗方法对其的影响.方法 应用四色流式细胞仪检测55例MG患者(治疗前)与33名健康对照外周血CD+4 CDhigh25 T细胞百分率,对其中26例MG患者进行了治疗前后的动态检测.结果 MG患者与健康对照外周血CD+4 CDhigh25 T细胞百分率分别为6.22%±3.37%与5.16%±1.87%,两者差异无统计学意义(P=0.061),而21例非手术治疗患者其外周血CD+4 CDhigh25 T细胞百分率的变化与病情评分的变化呈负相关(r=-0.563, P=0.008).结论 这种非手术治疗前后短期内的CD+4 CDhigh25 T细胞的变化情况可能与病情相关,但胸腺切除前阶段观察的情况有所不同.     

Elevated cerebrospinal fluid CD4/CD8 T cell ratio in myasthenia gravis

The proportions of CD2+, CD4+ and CD8+ lymphocytes were determined with the 3-layer indirect immunoperoxidase technique in the cerebrospinal fluid (CSF) of 31 patients with myasthenia gravis (MG) and 21 control subjects without autoimmune or central nervous system (CNS) diseases. None of the MG patients were using immunosuppressive drugs and all were thymectomized shortly after CSF sampling. Analysis of the reference population showed that the percentage of CD4+ lymphocytes and accordingly the CD4+/CD8+ T cell ratio is normally higher in CSF than in peripheral blood (PB). Compared to the controls, the mean percentage of CD4+ lymphocytes and the mean CD4+/CD8+ ratio in CSF were significantly higher in MG patients. In addition, the CD4+/CD8+ ratio was elevated in the CSF of 15 MG patients (48%) as a result of an elevation in the proportion of CD4+ and/or a decrease in CD8+ T cells. Among MG subjects the mean proportion of CD4+ lymphocytes was higher in the CSF of patients with also an elevated number of enlarged stimulated lymphoid cells in their CSF, which implies that these lymphocytes are often of the CD4+ phenotype. The percentage of CD4+ T cells in CSF was significantly higher in MG patients with a hyperplastic thymus or a thymoma than in those with an involuted thymus. Neither in MG patients nor in the reference population could an association be observed between CSF and PB lymphocyte subsets. In the controls this suggests that immunologic events of the CNS are normally not directly reflected in PB.(ABSTRACT TRUNCATED AT 250 WORDS)     

Benefits of FK 506 for refractory eye symptoms in a young child with ocular myasthenia gravis

Recently, there have been many reports on the efficacy and safety of tacrolimus (FK506) treatment for adult patients with intractable generalized myasthenia gravis (MG). There have also been a few reports of successful FK506 therapy in patients with severe childhood-onset generalized MG involving a myasthenic crisis. Herein, we report the efficacy of FK 506 for refractory ocular symptoms in a 3-year-old girl with ocular type MG. Ptosis and alternating strabismus had appeared at 10 months of age. No bulbar signs, respiratory failure or generalized muscle weakness had been seen during her course. Her ocular symptoms had persisted despite repeated steroid pulse therapy, high dose oral prednisolone and thymectomy. Adverse effects of steroids, including obesity, growth retardation, osteoporosis, cataracts and hyperlipidemia, gradually worsened. After obtaining written informed consent from her parents, we started oral tacrolimus at a dose of 0.5 mg/day and her symptoms resolved completely within 3 weeks at a maximum dose of 2.5 mg/day. No adverse effects, such as renal failure or glucose intolerance, were seen. FK506 treatment allowed the steroid dose to be reduced, eliminating its adverse effects. In patients with intractable childhood-onset MG with ocular manifestations, FK506 is an alternative to steroid therapy or thymectomy.     

重症肌无力患者外周血T淋巴细胞亚群凋亡的研究

目的探讨外周血T淋巴细胞亚群凋亡在重症肌无力(MG)免疫发病机制中的作用及临床意义。方法采用流式细胞术结合免疫荧光抗体法测定了45例MG患者和40例正常对照组外周血CD4~ T淋巴细胞、CD8~ T淋巴细胞百分数及其凋亡状况,并对24例MG患者在应用糖皮质激素治疗后外周血T淋巴细胞亚群凋亡状况进行了观察。结果MG患者组外周血CD8~ T淋巴细胞百分率较正常对照组明显降低,CD4~ /CD8~ 比值较正常对照组明显升高：MG患者组外周血CD4~ T淋巴细胞凋亡程度较正常对照组明显降低；MG患者外周血CD4~ T淋巴细胞凋亡程度与MG类型、预后密切相关：应用糖皮质激素治疗后MG患者外周血CD4~ T淋巴细胞凋亡程度明显增强。结论MG患者存在T淋巴细胞亚群的分布异常及CD4~ T淋巴细胞凋亡功能障碍,其凋亡程度可能与MG类型、预后密切相关,糖皮质激素对MG患者外周血CD4~ T淋巴细胞凋亡缺陷具有纠正作用。     

重症肌无力T细胞受体基因重排的检测及其临床意义

目的胸腺病变情况与重症肌无力患者的治疗及预后密切相关，为了能早期诊断胸腺瘤。方法用Ｓｏｕｔｈｅｒｎ杂交，分别以ＴＣＲ－α、β及γ为探针检测了一组重症肌力无力患者Ｔ细胞受体（ＴＣＲ）基因重排。结果６例患者ＤＮＡ经ＥｃｏＲＩ酶切，与ＴＣＲ－α、β探针杂交时有一条异常的重排带。这６例患者已４例经手术证实为胸腺肿瘤。结论ＴＣＲ基因重排可能为早期诊断胸腺瘤提供帮助。     

The effect of prednisone on the progression from ocular to generalized myasthenia gravis

Fifty percent of ocular myasthenia gravis (OMG) patients will progress to generalized myasthenia, 90% within 3 years from the onset of ocular symptoms. This study was performed to determine whether treatment with oral prednisone initiated and completed within 2 years from the onset of ocular symptoms would affect the progression of ocular myasthenia to generalized myasthenia gravis (GMG). Fifty-six patients were included in this review, with 27 patients in the prednisone-treated group and 29 patients in the untreated group. The treated group was initiated on 60 mg of prednisone daily with a slow taper over 3-6 months. At 2 years, significantly fewer patients in the treated group (3 of 27) progressed to generalized myasthenia when compared to the untreated group (10 of 29) (chi(2), p=0.04). Our results suggest that the early use of steroids may decrease progression of ocular to generalized myasthenia gravis. The decision to use steroids should be considered early in the course of patients diagnosed with ocular myasthenia gravis. This study should be considered preliminary and a prospective trial is warranted to confirm our observations.     

眼肌型重症肌无力进展为全身型重症肌无力的临床相关因素分析

目的 :探讨眼肌型重症肌无力进展为全身型重症肌无力的临床相关预测因素。方法 :33例初诊为眼肌型重症肌无力的患者经过3年随访,根据疾病进展结局分为眼肌型重症肌无力组(13例)和进展为全身型重症肌无力组(20例)。对与疾病进展可能相关的临床因素进行分析。结果 :进展为全身型重症肌无力组患者初诊时的定量重症肌无力评分、乙酰胆碱受体抗体阳性率、抗核抗体阳性率、合并胸腺瘤的比例以及合并糖尿病的比例均高于眼肌型重症肌无力组(P值均0.05)。结论 :定量重症肌无力评分高、乙酰胆碱受体抗体阳性、抗核抗体阳性以及合并胸腺瘤和糖尿病可能是眼肌型重症肌无力进展为全身型重症肌无力的预测指标。     

小儿眼型重症肌无力向全身型转化的临床特点

目的 研究小儿眼型重症肌无力(ocular myasthenia gravis,OMG)向全身型重症肌无力(generalized myasthenia gravis,GMG)的转型率、转型时间及使用泼尼松对转型的影响.方法 回顾性分析1977至2005年青岛大学医学院附属医院诊治的978例小儿OMG转变为GMG的转型率、转型时间以及泼尼松对转型的影响,并与同期诊治的1359例成人OMG患者进行对比分析.结果 小儿OMG转化为GMG的转型率为13.0%(127/978),而成人OMG的转型率为67.2%(913/1359),两组差异有统计学意义(χ2=674.17,P<0.01).OMG的转型时间大多在发病后的2年内,小儿OMG(58.3%,74/127)与成人OMG(83.6%,763/913)在发病后2年内转型的比率差异有统计学意义(χ2=45.39,P<0.01).使用泼尼松的456例小儿OMG患者中仅有5例(1.1%)转为GMG,而从未使用过泼尼松的522例小儿OMG患者中有122例(23.4%)变为GMG,差异有统计学意义(χ2=104.9,P<0.01).结论 小儿OMG转型率与成人OMG相比显著减少;转型的时间大多在发病后头2年内;泼尼松确实能减少小儿OMG向GMG转化的机会.     

Myasthenia gravis: Antibodies to acetylcholine receptor in ocular myasthenia gravis

Summary To improve the sensitivity of the radioimmunoassay method for anti-AChR-antibody, large amounts of sera from patients with myasthenia gravis, and higher concentrations of antigens and rabbit anti-human-IgG-antiserum, were used. These procedures enabled measurement of the titre value of over 0.04 pmol/ml serum and this value revealed a sensitivity about 10 times higher than that predicted using the previous model.Antibodies against AChR were found in 13 out of 17 ocular myasthenia patients (70%) and 35 of 37 with generalized myasthenia (90%). However, the average titre value of sera in those with ocular myasthenia was significantly lower than the value obtained in the generalized cases. Even in the patients with ptosis or ophthalmoparesis, in the early stage (less than one year) of ocular myasthenia, anti-AChR-antibodies were not detectable using this more sensitive assay method.

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Zusammenfassung Um die Empfindlichkeit der Radioimmunoassay-Methode für Anti-AChR-Antikörper zu verbessern, wurden eine große Menge des myasthenischen Serums, höhere Konzentration des Antigens und Kaninchen-Anti-Menschen-IgG-Antiserum gebraucht.Mit dieser Methode konnten wir den Wert über 0.04 pmol/ml Serum vermessen. Diese neue Methode zeigt etwa zehnfach höhere Empfindlichkeit als die vergangenen Methoden.Antikörper gegen AChR waren in 13 von 17 okulären Myastheniepatienten (70%) und in 35 von 37 generalisierten Myastheniepatienten (90%) gefunden worden. Aber der durchschnittliche Messungswert des Serums im Patienten der okulären Form war signifikant niedriger als der der generlisierten Form. Wenn der Patient auch Augenptose oder Augenparese hatte, waren die Anti-AChR-Antikörper mit unserer empfindlichen Methode im Frühstadium (innerhalb eines Jahres) nicht nachgewiesen worden.

     

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。     

成人重症肌无力由眼外肌向全身型的演化

目的 观察成人重症肌无力(MG)由眼外肌向全身演化的比例、时间及应用肾上腺糖皮质激素对病程和转归的影响.方法 对2005年1月至2012年1月我院诊治的以眼外肌受累为首发症状的成人MG 456例进行3个月至17年随访的回顾性研究,分析其临床演化的比例、时间及应用肾上腺皮质激素对转归的影响.结果 (1)共有197例(43.2％)在随诊期间演化成全身型MG,58.4％(115/197)在眼外肌症状发病1年内,74.1％(146/197)在2年内,80.7％(159/197)在3年内演化为全身型.其中171例(86.8％)演化为Ⅱa或Ⅱb型.(2)未应用激素治疗组(n=223)中134例演化为全身型MG(57.5％),较激素治疗组(63/233,28.3％)高(x2 =38.57,P＜0.01).在不同的时间段两组转化率差异无统计学意义.两组在演化后的最终Osserman分型差异也无统计学意义.结论 成年人以眼外肌发病的MG易发展为全身型,应用激素组较未应用激素组演化率低.     

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。     

Double filtration plasmapheresis benefits myasthenia gravis patients through an immunomodulatory action

Double filtration plasmapheresis (DFPP) is used to treat myasthenia gravis (MG). However, the definite mechanism is unclear. This study investigated whether DFPP improves MG through an immunomodulatory action. Thirty-five MG patients were randomly divided into two treatment groups: Group A (DFPP combined with oral methylprednisolone) and Group B (oral methylprednisolone alone). Their antibody levels, clinical scores, cytokine levels, and CD4⁺CD25^highFoxp3⁺ (regulatory T cell [Treg]) levels were then determined. Anti-titin antibody levels were significantly lower in Group A compared with Group B after treatment. The clinical remission rate in Group A was significantly higher than in Group B. The changes in cytokine levels (interleukin [IL]-2, IL-4, IL-10, and interferon-γ) in sera and the peripheral blood mononuclear cell culture supernatants did not significantly differ before and after the treatments in both groups (p < 0.05). The soluble intercellular adhesion molecule-1 (sICAM-1) levels were lower in Group A than in Group B (p < 0.05). MG patients exhibited a lower percentage of Treg cells than normal patients. DFPP combined with methylprednisolone treatment increased the Treg cell percentage more than treatment with methylprednisolone alone (p < 0.05). DFPP treatment more effectively lowers sICAM-1 and increases Treg cell expression, consequently benefiting MG patients.     

重症肌无力患者外周血CD_4~+CD_(25)~(high)T细胞及其动态观察

目的研究重症肌无力(myastheniagravis,MG)患者外周血CD4+CDh25ighT细胞的水平,以及各种治疗方法对其的影响。方法应用四色流式细胞仪检测55例MG患者(治疗前)与33名健康对照外周血CD4+CDh25ighT细胞百分率,对其中26例MG患者进行了治疗前后的动态检测。结果MG患者与健康对照外周血CD4+CD2h5ighT细胞百分率分别为6·22%±3·37%与5·16%±1·87%,两者差异无统计学意义(P=0·061),而21例非手术治疗患者其外周血CD4+CD2h5ighT细胞百分率的变化与病情评分的变化呈负相关(r=-0·563,P=0·008)。结论这种非手术治疗前后短期内的CD4+CD2h5ighT细胞的变化情况可能与病情相关,但胸腺切除前阶段观察的情况有所不同。     

眼肌型重症肌无力临床分析

目的总结分析眼肌型重症肌无力患者的临床特征,以为诊断和治疗提供参考依据。方法回顾性分析113例眼肌型重症肌无力患者的临床资料。采用免疫荧光细胞染色方法检测血清乙酰胆碱受体(AChR)抗体和肌肉特异性受体酪氨酸激酶(MuSK)抗体表达水平,分析这两项免疫学指标对眼肌型重症肌无力向全身型转化的预测价值。结果成年发病的眼肌型重症肌无力好发于40岁以上男性,多以眼睑下垂(95例,84.07%)为首发症状,少数以复视(18例,1 5.93%)起病。疲劳试验和新斯的明试验阳性率分别为79.44%(85/107)和84.85%(84/99),低频重复神经电刺激和血清甲状腺抗体异常率分别为44.32%(39/88)和28%(14/50),胸腺增生和胸腺瘤阳性率分别为16.67%(17/102)和11.76%(12/102);血清AChR抗体阳性率为62.83%(71/113);但MuSK抗体均呈阴性。眼肌型重症肌无力向全身型转化率为12.39%(14/113),其中血清AChR抗体强阳性者(13例,28.26%)显著高于弱阳性者(1例,4%),二者差异有统计学意义(X~2=4.587,P=0.032)。结论成年发病的眼肌型重症肌无力好发于中年以上男性,主要表现为眼睑下垂和复视,大多数患者伴发胸腺和甲状腺异常。血清AChR抗体表达水平升高预示向全身型转化率升高,鲜有MuSK抗体阳性反应。     

眼肌型重症肌无力临床分析

目的总结分析眼肌型重症肌无力患者的临床特征,以为诊断和治疗提供参考依据。方法回顾性分析113例眼肌型重症肌无力患者的临床资料。采用免疫荧光细胞染色方法检测血清乙酰胆碱受体（AChR）抗体和肌肉特异性受体酪氨酸激酶（MuSK）抗体表达水平,分析这两项免疫学指标对眼肌型重症肌无力向全身型转化的预测价值。结果成年发病的眼肌型重症肌无力好发于40岁以上男性,多以眼睑下垂（95例,84．07％）为首发症状,少数以复视（18例,15．93％）起病。疲劳试验和新斯的明试验阳性率分别为79．44％（85／107）和84．85％（84／99）．低频重复神经电刺激和血清甲状腺抗体异常率分别为44．32％（39／88）和28％（14／50）,胸腺增生和胸腺瘤阳性率分别为16．67％（17／102）和11．76％（12／102）;血清AChR抗体阳性率为62.83％（71／113）;但MuSK抗体均呈阴性。眼肌型重症肌无力向全身型转化率为12．39％（14／113）,其中血清AChR抗体强阳性者（13例,28．26％）显著高于弱阳性者（1例,4％）,二者差异有统计学意义（X^2=4．587,P=0．032）。结论成年发病的眼肌型重症肌无力好发于中年以上男性,主要表现为眼睑下垂和复视,大多数患者伴发胸腺和甲状腺异常。血清AChR抗体表达水平升高预示向全身型转化率升高,鲜有MuSK抗体阳性反应。     

Giant cell polymyositis associated with myasthenia gravis and thymoma

We report a case of a 40-year-old woman who developed generalized muscle weakness over a period of 2 months. Physical examination revealed palpable masses in her arms and hands. Serum creatine kinase levels were elevated. Electromyography showed myopathic changes and 3 Hz repetitive nerve stimulation revealed a decremental pattern on repetitive nerve stimulation. Muscle MRI demonstrated increased signal intensity in the biceps brachii on T1-weighted images. Chest CT scan showed a mediastinal mass suggestive of thymoma. Muscle biopsy revealed giant cell polymyositis. The patient was treated with cholinesterase inhibitors and corticosteroids with improvement of strength, and subsequently underwent thymectomy followed by radiotherapy.     

眼肌型重症肌无力的临床治疗

目的 比较激素和溴吡斯的明在眼肌型重症肌无力(MG)患者中的不同疗效,寻找最佳治疗方法.方法 对2001年12月至2009年1月就诊的初次发病的43例眼肌型MG患者资料进行回顾性研究,根据治疗方式分为溴吡斯的明治疗(A)组6例,溴吡斯的明无效后改用泼尼松治疗(B)组16例,泼尼松治疗(C)组21例,分别选择MG临床绝对评分法的眼肌功能评分和相对评分法对每种治疗方法的疗效进行量化比较.结果 泼尼松治疗期(B+C)前后绝对评分差为7.86±4.28,溴吡斯的明治疗期(A+B)为2.64±2.52(t=-5.2,P<0.01);两者的相对评分(分别为0.76±0.32和0.31±0.30,Z=-4.72,P<0.01)及复发病例数(分别为12例和13例,χ~2=4.02,P=0.045)差异有统计学意义.B组和C组治疗前后疗效无明显差异.结论 激素治疗眼肌型MG的效果优于溴吡斯的明,半年内激素治疗的早晚对治疗效果可能无明显影响.     

眼肌无力的诊断及依据

重症肌无力是乙酰胆碱受体抗体介导的,细胞免疫依赖及补体参与的神经-肌肉接头处（NMJ）传递障碍的自身免疫性疾病。眼肌症状是最为多见的首发症状,表现为上眼睑下垂、复视、斜视等,尤以眼睑下垂最多。通过典型的临床表现及临床实验即可诊断、腾喜龙试验、血清抗体检测、电子诊断可以进一步确诊。