重症肌无力相关抗体的研究进展

作为一种累及神经肌肉接头的自身免疫性疾病,重症肌无力(myasthenia gravis,MG)的发病机制与自身免疫性抗体密切相关。关于MG相关抗体,研究最多且最为明确的是乙酰胆碱受体抗体(acetylcholine receptor antibody,AChR-Ab),由于存在AChR-Ab阴性的MG患者,近年来学者们开始热衷于研究AChR-Ab以外的其他抗体,如肌肉特异性酪氨酸激酶抗体、低密度脂蛋白4抗体等,并进行相应治疗方案的探索。该文对MG相关抗体的研究进展进行综述,为今后治疗该病提供临床依据和参考。     

Neurologic Complications of Immune Checkpoint Inhibitors in Thoracic Malignancies

Immune checkpoint inhibitors (ICIs) have transformed the prognosis of cancers previously considered lethal. The spectrum of therapeutic indications is rapidly expanding, including the vast majority of thoracic malignancies. By enhancing the immune responses against cancer, the ICI treatments lead to the development of immune-related adverse events (irAEs) that may affect any organ. Severity varies from mild to fatal clinical manifestations. Neurologic involvement is relatively rare and highly heterogeneous, including central and peripheral nervous system diseases associated with neural-specific autoantibodies or not, central nervous system vasculitis, and granulomatous and demyelinating disorders. Symptoms often manifest within the first four cycles of treatment and can develop regardless of the class of ICI used. An unfavorable outcome is found in up to one-third of patients and is generally associated with the patients’ clinical characteristics (e.g., age, coexistence of systemic adverse events), cancer type (e.g., lung cancer versus other), and specific clinical setting (e.g., ICI treatment in patients with preexisting paraneoplastic neurologic autoimmunity, ICI rechallenge after a first neurologic irAE). Diagnosis should be suspected in patients with new-onset neurologic symptoms while on ICI treatment which are not explained by metastatic disease or other metabolic/infectious disorders. Recommended treatment is based on clinical severity and consists of ICI discontinuation with or without immunosuppressive/immunomodulatory therapy, although alternative approaches are reasonable depending on cancer status (e.g., aggressive immunosuppression without discontinuing ICI in patients with initial cancer response). Early recognition and appropriate treatment of these neurologic irAEs are crucial for improved patient outcomes and therapeutic planning.     

Myasthenia Gravis Appearing After Thymectomy: a Case Report and Review of the Literature

A small proportion of thymoma patients without myasthenia gravis (MG) have been observed to develop MG after total removal of the thymoma. However, the underlying cause is not yet known due to the rarity of postoperative MG patients. We report a 39-year-old man in whom MG appeared after surgical removal of a thymoma. Computed tomography and magnetic resonance imaging showed no signs of recurrent or metastatic thymoma. Administration of pyridostigmine bromide resulted in the prompt improvement of myasthenic symptoms. Our observations indicate that postoperative follow-up care with monitoring of possible postoperative MG is necessary after resecting a thymoma.     

电视胸腔镜辅助胸腺切除术

目的探讨电视胸腔镜辅助胸腺切除的临床应用价值. 方法 2002年9月～2004年6月,18例胸腺疾病和重症肌无力(myasthenia gravis,MG)行胸腔镜辅助下胸腺切除手术,其中胸腺全切7例,11例MG行胸腺扩大切除. 结果 17例在胸腔镜辅助下完成, 1例中转小切口(7 cm)开胸手术.3例MG术后须短暂呼吸机辅助通气(<12 h),二次气管插管1例,余无严重并发症,无手术死亡.手术时间47～115 min,平均95 min;胸腔引流时间1.2～2.6 d,平均2 d;术后住院时间4～9 d,平均5.5 d.9例良性胸腺瘤或胸腺囊肿随访3～20个月,平均13个月,无复发.11例MG随访3～19个月,平均10个月,4例症状完全缓解,7例都分缓解. 结论胸腔镜辅助下胸腺切除手术,具有创伤小、恢复快等优点,胸腔镜下胸腺扩大切除治疗重症肌无力在技术上是可行的.     

重症肌无力中枢神经系统受损模型

目的近年研究结果表明，重症肌无力（ＭＧ）病变部位并不仅仅局限于神经肌接头（ＮＭＪ）处突触后膜烟碱型乙酰胆碱受体（ｎＡＣｈＲ），烟碱型乙酰胆碱受体抗体（ＡＣｈＲ－ａｂ）病理作用可能波及到中枢神经系统（ＣＮＳ）。因此，有必要建立模拟ＭＧ患者ＣＮＳ损害的动物模型，研究ＭＧ患者脑脊液中存在的ＡＣｈＲ－ａｂ引起ＣＮＳ损害的机制。方法从ＭＧ患者血中提取的ＡＣｈＲ－ａｂ经侧脑室穿刺注入到大鼠脑室系统，然后观察其症状和体征，以及用脑干听觉诱发电位仪（ＢＡＥＰ）检测鼠脑干听觉传导中枢功能。用免疫组化法（ＡＢＣ）研究ＡＣｈＲ－ａｂ与ＣＮＳ神经－ｎＡＣｈＲ之间免疫结合反应及其分布。结果大鼠除了出现脑干听觉传导中枢功能障碍外，还出现类似于ＭＧ动物模型表现的症状。免疫组化研究结果显示，神经－ｎＡＣｈＲ样阳性免疫反应广泛分布于ＣＮＳ许多部位。结论脑室内注入的ＡＣｈＲ－ａｂ与神经－ＡＣｈＲ结合引起ＣＮＳ功能障碍和出现ＭＧ动物模型样症状。我们首次建立的中枢受损的ＭＧ模型将有助于阐明ＡＣｈＲ－ａｂ引起中枢受损和ＣＮＳ下位运动神经元引起横纹肌收缩无力的机制。     

The thymus in seronegative myasthenia gravis patients

Summary In 5–10% of all patients with typical generalised myasthenia gravis (MG), serum antibody to the acetylcholine receptor (AChR) is undetectable. To determine whether these represent a distinct subgroup, we have compared the thymuses of 14 seronegatives, 70 seropositives and 12 non-myasthenic controls. By quantitative immunohistology on coded sections, the 7 seronegative samples were clearly distinguishable from the controls by the pronounced lymph node-type T-cell areas in the medulla. While these closely resembled those in the seropositive cases, germinal centres were significantly sparser, and total in vitro IgG production was disproportionately low (per B cell) in the 12 cases tested. Furthermore, specific anti-AChR production was never detected in any of these cultures. The data support the view that the medullary T-cell areas are the most consistent abnormalitiy in the MG thymus (though it may not be primary), and they strongly imply that seronegative and seropositive MG are distinct entities.     

新胆碱酯酶抑制剂对实验性重症肌无力的治疗作用

本文应用实验性重症肌无力模型研究了7种新的胆碱酯酶抑制剂对实验性重症肌无力的治疗作用,其中包括6种二甲氨基甲酸烷氧(烷硫)基苯酯及1种中草药提取物,大多数化合物对乙酰胆碱酯酶有较强的抑制作用,并见到有不同程度的治疗效果。二甲氨基甲酸-3-叔丁基-4〔2-(1-哌啶基)乙氧基〕苯酯不仅明显改善肌无力症状,而且毒性小、副作用较新斯的明轻,值得进一步研究。     

伴重症肌无力的胸腺瘤HLA类分子表达强度分析

目的 通过比较伴重症肌无力(MG)的胸腺瘤、单纯胸腺瘤和正常胸腺中HLA类分子表达强度的差异，探讨伴MG胸腺瘤内异常微环境因素。方法 采用免疫组化方法检测HLA-Ⅰ(A、B、C)和HLA-DR表达，光镜下扫描图像入计算机，处理后得HLA类分子染色的积分光密度以分析其表达强度。结果 皮质型胸腺瘤HLA-DR表达强度减弱，伴MG皮质型胸腺瘤HLA-DR表达强度减弱程度更甚。结论 伴MG的皮质型胸腺瘤表达HLA-DR强度减弱可能是其内的胸腺细胞分化、发育异常的原因，可能与MG发病相关。     

电视胸腔镜胸腺切除治疗重症肌无力症

目的探讨电视胸腔镜手术(video-assisted thoracoscopic surgery,VATS)胸腺切除治疗重症肌无力症(myasthenia gravis,MG)的可行性. 方法 18例MG采用VATS经右胸前侧径路行胸腺切除联合纵隔脂肪清扫. 结果 17例顺利完成手术,1例因电凝钩伤及左头臂静脉干而中转开胸止血.平均手术时间105 min,术中失血量平均80 ml.全组无术后死亡及危象发生.18例随访1～20个月,平均11.3个月.按Osserman疗效评价,缓解5例(27.8%),明显改善6例(33.3%),部分改善4例(22.2%),无变化3例(16.7%),有效率83.3%(15/18). 结论 VATS经右胸前侧径路行完全胸腺切除可行,且具有创伤小、恢复快等优点.