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某些免疫抑制程序对重症肌无力的影响。

Effects of some immunosuppressive procedures on myasthenia gravis.

作者信息

Matell G, Bergström K, Franksson C, Hammarström L, Lefvert A K, Möller E, von Reis G, Smith E

出版信息

Ann N Y Acad Sci. 1976;274:659-76. doi: 10.1111/j.1749-6632.1976.tb47724.x.

Abstract

Clinical Observations. A total of 53 MG patients have been treated with different immunosuppressive methods (alone or combined) with the following effects: Thymectomy was performed in 38 patients. The improvement was excellent in 15, and moderate or uncertain in 20. In three patients severe long-lasting deterioration followed the operation. ACTH treatment (n=32): Initial deterioration during the 5-7 days of heavy ACTH treatment (1000 IU) was followed by an improvement lasting on an average 4 months. The improvement was good or moderate in 78% of the patients. Betamethazone treatment has been tried in six patients where ACTH and azathioprine was ineffective. In four of these patients the results were excellent. Azathioprine treatment has been given to 26 patients for periods up to 7 years. An improvement is measurable after 6-12 weeks and it seems maximal after about 1 year. Of the 26, 80% responded favorable with reduction in the need for cholinesterase inhibitors. Severe complications were seen in three patients with one death. Drainage of thoracic duct lymph was initiated in 14 patients up to 4 weeks with rapid improvement lasting as long as drainage was performed. Long-termed effects of the drainage may be present, however. Retransfusion of homologous cell-free lymph precipitated a return of the myasthenic symptoms. Biochemical Studies on Myasthenic Lymph. Using a membrane preparation from the electric organ from Torpedo marmorata and tritiated Naja naja siamensis neurotoxin we demonstrated a decreasing binding of toxin to the receptor in the presence of MG lymph gamma-globulin fraction. Gammaglobulins from controls showed almost no inhibition of the neurotoxin binding. Immunological Studies. An increased frequency of HL-A1 and 8 was found in female patients. LD typing was also performed. During a period of three weeks of thoracic duct drainage 130X10(9) or about 10% of total number of lymphocytes in the body were removed. In the lymph an initial decrease in the proportion of thymus-derived lymphocytes (T cells) occurred, which was accompanied by a sequent increase in the proportion of bone-marrow-derived lymphocytes (B cells). Towards the end of drainage this effect was reverted. Mitogenic stimulation using lymphocytes from thoracic duct drainage revealed no differences as compared to normal cells. The proportions of T and B cells was studied in the peripheral blood in nine patients treated with ACTH. During treatment there was an initial decrease in the proportion of T cells accompanied by a subsequent rise in the proportion of B cells, which was maximal after 3-10 days. These proportions were reverted to normal 1-5 days after the maximal change. The effect of azathioprine on T and B cells has also been studied.

摘要

临床观察。共有53例重症肌无力(MG)患者接受了不同的免疫抑制方法治疗(单独使用或联合使用),效果如下:38例患者接受了胸腺切除术。其中15例改善明显,20例改善程度中等或效果不确切。3例患者术后出现严重且持久的病情恶化。促肾上腺皮质激素(ACTH)治疗(n = 32):在大剂量ACTH治疗(1000 IU)的5 - 7天内出现初始病情恶化,随后平均持续4个月的改善。78%的患者改善良好或中等。6例对ACTH和硫唑嘌呤无效的患者尝试了倍他米松治疗。其中4例患者效果极佳。26例患者接受硫唑嘌呤治疗长达7年。6 - 12周后可测量到改善,约1年后似乎达到最大效果。26例患者中,80%反应良好,胆碱酯酶抑制剂的需求减少。3例患者出现严重并发症,1例死亡。14例患者进行了胸导管淋巴引流,持续长达4周,引流期间病情迅速改善。然而,引流可能存在长期影响。回输同源无细胞淋巴导致肌无力症状复发。重症肌无力淋巴的生化研究。使用电鳐电器官的膜制剂和氚标记的眼镜蛇神经毒素,我们证明在存在MG淋巴γ球蛋白组分的情况下,毒素与受体的结合减少。对照组的γ球蛋白几乎不抑制神经毒素的结合。免疫学研究。在女性患者中发现人类白细胞抗原(HL - A)1和8的频率增加。还进行了LD分型。在胸导管引流的三周期间,清除了130×10⁹个淋巴细胞,约占体内淋巴细胞总数的10%。在淋巴中,胸腺来源的淋巴细胞(T细胞)比例最初下降,随后骨髓来源的淋巴细胞(B细胞)比例随之增加。在引流接近尾声时,这种效应逆转。使用胸导管引流的淋巴细胞进行促有丝分裂刺激,与正常细胞相比未发现差异。研究了9例接受ACTH治疗患者外周血中T细胞和B细胞的比例。治疗期间,T细胞比例最初下降,随后B细胞比例上升,在3 - 10天后达到最大值。这些比例在最大变化后的1 - 5天恢复正常。还研究了硫唑嘌呤对T细胞和B细胞的影响。

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