Dalakas Marinos C
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA.
Clin Rev Allergy Immunol. 2005 Dec;29(3):255-69. doi: 10.1385/CRIAI:29:3:255.
Controlled trials with intravenous immunoglobulin (IVIg) were conducted in patients with Stiff-Person Syndrome (SPS) and dermatomyositis (DM), two humorally mediated neurological disorders, and in inclusion body myositis (IBM), a T-cell-mediated inflammatory myopathy. The clinical efficacy was compared with alterations on tissue expression of complement, cytokines, chemokines, adhesion molecules, and immunoregulatory genes. The following patients were randomized in three separate trials to receive IVIg or placebo for 3 mo: (a) 16 patients with anti-GAD antibody-positive SPS; (b) 15 patients with DM resistant to therapies; and (c) 19 patients with IBM. After a washout, they crossed to the alternative therapy for another 3 mo. Efficacy was based on the difference in the respective disease scores from baseline to the second and third month of the infusions. In patients with SPS and DM, the scores changed positively and significantly from months 1 through 3, but returned to baseline when the patients crossed to placebo. In contrast, the scores in the placebo-randomized group remained constant or worsened from months 1 to 3, but improved significantly after crossing to IVIg. The muscle scores of patients with IBM did not significantly change between IVIg or placebo. In SPS, the anti-GAD65 antibody titers declined after IVIg but not after placebo. In DM, there was reduction of complement consumption, interception of membranolytic attack complex formation, downregulation of inflammation, fibrosis, cytokines, chemokines and adhesion molecules, and alterations in thousands of immunoregulatory genes. We conclude that IVIg is a safe and effective therapy for patients with SPS and DM unresponsive to other agents. In tissues, IVIg restores tissue cytoarchitecture by suppressing the inflammatory mediators at the protein, mRNA, and gene level.
对患有僵人综合征(SPS)和皮肌炎(DM)这两种体液介导的神经疾病的患者,以及患有包涵体肌炎(IBM)这种T细胞介导的炎性肌病的患者进行了静脉注射免疫球蛋白(IVIg)的对照试验。将临床疗效与补体、细胞因子、趋化因子、黏附分子和免疫调节基因的组织表达变化进行了比较。在三项独立试验中,以下患者被随机分组,接受3个月的IVIg或安慰剂治疗:(a)16例抗谷氨酸脱羧酶(GAD)抗体阳性的SPS患者;(b)15例对治疗耐药的DM患者;(c)19例IBM患者。经过洗脱期后,他们交叉接受另一种治疗3个月。疗效基于从基线到输注的第二个月和第三个月各自疾病评分的差异。在SPS和DM患者中,从第1个月到第3个月评分呈正向且显著变化,但当患者交叉接受安慰剂治疗时,评分又回到了基线。相比之下,安慰剂随机分组组的评分从第1个月到第3个月保持不变或恶化,但在交叉接受IVIg治疗后显著改善。IBM患者的肌肉评分在IVIg或安慰剂治疗之间没有显著变化。在SPS中,IVIg治疗后抗GAD65抗体滴度下降,而安慰剂治疗后未下降。在DM中,补体消耗减少,膜溶解攻击复合物形成被阻断,炎症、纤维化、细胞因子、趋化因子和黏附分子下调,以及数千个免疫调节基因发生改变。我们得出结论,IVIg对其他药物无反应的SPS和DM患者是一种安全有效的治疗方法。在组织中,IVIg通过在蛋白质、mRNA和基因水平抑制炎症介质来恢复组织细胞结构。