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IVIG efficacy in CIDP patients is not associated with terminal complement inhibition

机译:CIDP患者的IVIG疗效与终端补体抑制无关

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Patients with acute and chronic inflammatory demyelinating neuropathies exhibit elevated serum and cerebrospinal fluid (CSF) levels of terminal complement activation products and therapeutic inhibition of complement activation is currently tested for its safety and efficacy in patients with Guillain-Barre syndrome (GBS). Here, we determined serum levels of the complement activation products C3a, C5a and the soluble terminal complement complex (sTCC) in 39 individuals with chronic inflammatory demyelinating polyneuropathy (CIDP) who participated in one of the largest ever conducted clinical trial in patients with CIDP (ICE trial) and received Intravenous Immunoglobulin (IVIG) or placebo (albumin) in 3 week intervals for up to 24 weeks. In placebo-treated patients with spontaneous disease remission, serum sTCC levels moderately decreased over time. Levels of complement activation products were, however, not modulated by IVIG and remained unchanged in patients with a beneficial response to IVIG therapy as compared to those with steady or worsened disease. These results suggest that the therapeutic efficacy of IVIG in CIDP is based on immunomodulatory mechanisms different from complement inhibition. Terminal complement activation merits further investigation as a surrogate marker for disease progression and therapeutic target in patients with CIDP.
机译:急性和慢性炎症脱髓鞘神经病的患者表现出升高的血清和脑脊液(CSF)末端补体激活产物的水平,目前对患有Guillain-Barre综合征(GBS)的患者的安全性和功效进行治疗抑制。在这里,我们确定在39个个体中的补体激活产物C3A,C5A和可溶性末端补体复合物(STC)的血清水平慢性炎症脱髓鞘(CIDP),他们参与了CIDP患者的最大临床试验之一( ICE试验)以3周的间隔以3周的间隔接受静脉内免疫球蛋白(IVIG)或安慰剂(白蛋白)。在安慰剂治疗的自发性疾病缓解患者中,随着时间的推移,血清STCC水平适度下降。然而,与具有稳定或恶化的疾病的人相比,补体激活产物的水平未被IVIG调节,并且在对IVIG治疗的患者中保持不变。这些结果表明,IVIG在CIDP中的治疗效果基于免疫调节机制不同于补体抑制。末端补充激活优异的优点进一步调查作为CIDP患者的疾病进展和治疗靶标的替代标志物。

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