Schubothe H, Maas D, Weber S, Raif W, Marsovsky E, Herberg D
Immun Infekt. 1982 Nov;10(6):230-9.
Long-term studies on 11 patients suffering from methyldopa-induced autoimmune haemolytic anaemia suggest that this self limitable episode of disturbed immune tolerance is characterized by five main parameters: 1. The autoimmune pathogenic average daily drug dose: Unfortunately, it cannot be estimated exactly due to the individually rather variable absorption of methyldopa (7-62%). The lowest oral dose in our patients was 125 mg daily. 2. The period of autoimmune induction: between the start of the methyldopa administration and the beginning of autoantibody production. It has to be estimated somewhat shorter than the time up to the clinical manifestation of the haemolytic anaemia. This varied over a wide range from 2 to 52 months. 3. The period of the active autohemolysis: between the appearance of pathogenic autoantibodies and the withdrawal of methyldopa. It depends on the recognition of the cause of the disease. In our patients it varied between 2 and 32 weeks. 4. The period of the haematologic remission: between the withdrawal of methyldopa and the normalization of the red blood cell values. It ranged between 4 weeks and 4 months. Contrary to the other parameters, the clinical remission is almost uniform in all patients. It begins immediately when the drug is stopped. This fact suggests that the induction and maintenance of the disease needs a continuous application of methyldopa and its presence in blood and tissue. The normalization of the red blood cell turnover simultaneous with the cessation of therapy, although the direct antiglobulin test remains positive, reveals a change of the autoantibodies into those apathogenic variants known from the majority of methyldopa-induced autoimmunizations. 5. The period of immunologic remission: between the withdrawal of methyldopa and the definite extinction of autoantibody production. It varied between 4 and 12 months. Transition to or later development of an autonomous warm autoantibody anaemia were not observed. The disease remits spontaneously. Its prompt reversibility resembles the same phenomenon in autoantibody anaemias induced by infectious agents. An inhibition of methyldopa-sensitive suppressor-T-cells may initiate the disturbed tolerance disease.
对11例甲基多巴诱发的自身免疫性溶血性贫血患者的长期研究表明,这种免疫耐受紊乱的自限性发作具有五个主要参数:1. 自身免疫致病的平均每日药物剂量:遗憾的是,由于甲基多巴的个体吸收差异较大(7%-62%),无法准确估算。我们患者中最低的口服剂量为每日125毫克。2. 自身免疫诱导期:从开始服用甲基多巴到自身抗体产生。估计此时间比直至溶血性贫血临床表现的时间略短。这一时期变化范围很广,从2个月到52个月不等。3. 活跃自身溶血期:从致病性自身抗体出现到停用甲基多巴。这取决于对病因的认识。在我们的患者中,此时期在2周和32周之间变化。4. 血液学缓解期:从停用甲基多巴到红细胞值恢复正常。此时期在4周和4个月之间。与其他参数相反,所有患者的临床缓解几乎一致。停药后立即开始。这一事实表明,疾病的诱导和维持需要持续应用甲基多巴以及其在血液和组织中的存在。治疗停止时红细胞周转率恢复正常,尽管直接抗球蛋白试验仍为阳性,这表明自身抗体已转变为大多数甲基多巴诱发的自身免疫反应中已知的无致病性变体。5. 免疫缓解期:从停用甲基多巴到自身抗体产生完全消失。此时期在4个月到12个月之间。未观察到向自主性温抗体贫血的转变或后期发展。疾病自发缓解。其迅速可逆性类似于感染因子诱发的自身抗体贫血中的相同现象。对甲基多巴敏感的抑制性T细胞的抑制可能引发免疫耐受紊乱疾病。