Bystryn Jean-Claude, Jiao Diane
The Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA.
Autoimmunity. 2006 Nov;39(7):601-7. doi: 10.1080/08916930600972016.
Intraveneous immunoglobulin (IVIg) is increasingly used to treat pemphigus vulgaris (PV). The mechanism by which it does so is not known. The following study was conducted to confirm the effectiveness of IVIg for the acute control of active PV and to elucidate the mechanism by which it does.
Twelve patients with active and severe PV unresponsive to conventional therapy with high doses of systemic steroids together with or without a cytotoxic drug were treated with a single dose of IVIg (400 mg/kg/day for 5 days). All patients were concurrently given cyclophosphamide or azathioprine of not already on one of these two drugs. The primary end-points were healing of skin lesions, changes in serum levels of intercelular (IC) autoantibodies and in steroid doses one to 3 weeks after initiation of IVIg.
Within 1 week of initiating IVIg the activity of PV was controlled in most cases. Within 3 weeks the average baseline dose of systemic steroid was reduced by 40%. Serum levels of IC antibodies rapidly declined by an average of 59% within 1 week of initiating IVIg and by 70% within 2 weeks. The decrease was selective, as the average serum levels of antibody to varicella-herpes zoster did not decrease in the 4 patients in whom they were measured. The decrease in IC antibodies was inversely related to serum levels of total inmmunoglobulin (IgG). The decrease in IC antibodies was not due to blocking factors in the IVIg preparation and was too rapid to be due to suppression of IgG synthesis, suggesting that it resulted from increased catabolism.
IVIg can rapidly control active PV unresponsive to conventional therapy by causing a selective and very rapid decline in the autoantibodies that mediate the disease. We believe it does so by increasing the catabolism of all serum IgG antibodies, and that this results in a selective decrease in only abnormal autoantibodies as catabolized normal anti bodies are replaced by those present in the IVIg preparation. IVIg is the first treatment that achieves the ideal therapeutic goal in auto-antibody diseases, the selective removal of the pathogenic antibodies without affecting the level of normal antibodies.
静脉注射免疫球蛋白（IVIg）越来越多地用于治疗寻常型天疱疮（PV）。其作用机制尚不清楚。开展以下研究以证实IVIg对急性控制活动期PV的有效性，并阐明其作用机制。
12例对高剂量全身性类固醇联合或不联合细胞毒性药物的传统治疗无反应的活动期重度PV患者接受单剂量IVIg治疗（400mg/kg/天，共5天）。所有患者同时给予环磷酰胺或硫唑嘌呤，前提是尚未使用这两种药物之一。主要终点为IVIg治疗开始后1至3周皮肤病变的愈合情况、细胞间（IC）自身抗体血清水平的变化以及类固醇剂量的变化。
在开始IVIg治疗的1周内，大多数病例中PV的活动得到控制。3周内，全身性类固醇的平均基线剂量降低了40%。在开始IVIg治疗的1周内，IC抗体的血清水平迅速下降，平均下降59%，2周内下降70%。这种下降具有选择性，因为在测量的4例患者中，水痘 - 带状疱疹抗体的平均血清水平没有下降。IC抗体的下降与总免疫球蛋白（IgG）的血清水平呈负相关。IC抗体的下降不是由于IVIg制剂中的封闭因子，且下降速度太快，不可能是由于IgG合成受到抑制，这表明其是由分解代谢增加所致。
IVIg可通过使介导该疾病的自身抗体选择性且非常迅速地下降，快速控制对传统治疗无反应的活动期PV。我们认为其通过增加所有血清IgG抗体的分解代谢来实现这一点，并且这导致仅异常自身抗体选择性下降，因为分解代谢的正常抗体被IVIg制剂中的抗体所取代。IVIg是第一种在自身抗体疾病中实现理想治疗目标的治疗方法，即选择性去除致病抗体而不影响正常抗体水平。
