Dalakas M C
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1382, USA.
Neurology. 1998 Dec;51(6 Suppl 5):S2-8. doi: 10.1212/wnl.51.6_suppl_5.s2.
On the basis of controlled clinical trials, high-dose intravenous immunoglobulin (IVIg) has emerged as a critical therapy in the management of patients with various autoimmune neurologic diseases. Different interpretations of the clinical trial results, the expected benefit of IVIg compared to that of alternate therapies, off-label use, results from anecdotal or empirical clinical trials, issues about safety and cost and, most importantly, the uncertainty about mechanisms of action of IVIg have generated concerns among practicing neurologists. Understanding the mechanisms of action of IVIg and its potential risks or side effects is expected to help us make more judicious use of this powerful immunodulating agent. This article provides evidence that IVIg has multiple actions which may operate in concert with each other but that for each disease a predominant mechanism may prevail according to the underlying immunopathogenetic cause of the respective disorder. The most relevant actions of IVIg in the therapy of neurological diseases include (a) inhibition of complement binding and prevention of MAC formation, (b) neutralization of certain pathogenic cytokines, (c) downregulation of antibody production, and (d) modulation of Fc-receptor mediated phagocytosis. Additional actions include the effect of Mg on superantigens, modulation of T-cell function and antigen recognition, and enhancement of remyelination. On the basis of our experience with more than 130 closely monitored patients, I provide guidelines on how to use the drug, kinetics of IVIg, adverse reactions, and risk factors. In addition, the incidence, morbidity prevention and treatment of the common or rare side effects, including thromboembolic events, increased serum viscosity, aseptic meningitis, headaches, skin reactions, renal failure, and hemolysis are described. Spurious results of serologic tests, such as false hyponatremia and elevated sedimentation rate, as well as a transient rise in various viral titers, are described in an effort to avoid misinterpretations by treating neurologists. Finally, details on the latest findings of viral safety of IVIg are provided.
基于对照临床试验，大剂量静脉注射免疫球蛋白（IVIg）已成为治疗各种自身免疫性神经疾病患者的关键疗法。对临床试验结果的不同解读、IVIg与替代疗法相比的预期益处、超适应症使用、来自轶事或经验性临床试验的结果、安全性和成本问题，以及最重要的是IVIg作用机制的不确定性，引发了神经科执业医生的担忧。了解IVIg的作用机制及其潜在风险或副作用，有望帮助我们更明智地使用这种强大的免疫调节剂。本文提供的证据表明，IVIg具有多种相互协同作用的效应，但对于每种疾病，根据各自疾病潜在的免疫发病机制，可能有一种主要机制起主导作用。IVIg在神经疾病治疗中最相关的作用包括：（a）抑制补体结合并防止膜攻击复合物（MAC）形成；（b）中和某些致病细胞因子；（c）下调抗体产生；（d）调节Fc受体介导的吞噬作用。其他作用包括镁对超抗原的作用、T细胞功能和抗原识别的调节，以及促进髓鞘再生。基于我们对130多名密切监测患者的经验，我提供了关于如何使用该药物、IVIg的动力学、不良反应和风险因素的指南。此外，还描述了常见或罕见副作用的发生率、发病预防和治疗，包括血栓栓塞事件、血清粘度增加、无菌性脑膜炎、头痛、皮肤反应、肾衰竭和溶血。还描述了血清学检测的假性结果，如假性低钠血症和血沉升高，以及各种病毒滴度的短暂升高，以避免治疗神经科医生的误解。最后，提供了关于IVIg病毒安全性最新发现的详细信息。
