Novel complement inhibitor limits severity of experimentally myasthenia gravis.
Novel complement inhibitor limits severity of experimentally myasthenia gravis.
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DOI：
10.1002/ana.21536
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发表时间：
2009-01
影响因子：
11.2
通讯作者：
Kaminski, Henry J.
中科院分区：
文献类型：
--
作者：
Soltys, Jindrich;Kusner, Linda L.;Young, Andrew;Richmonds, Chelliah;Hatala, Denise;Gong, Bendi;Shanmugavel, Vaithesh;Kaminski, Henry J.
补体介导的神经肌肉接头损伤被认为是人类重症肌无力和实验获得性重症肌无力（EAMG）动物模型的主要疾病机制。我们利用主动和被动EAMG模型，以研究一种新的C5补体抑制剂rEV 576，重组产生的蛋白质来自蜱唾液，在缓和疾病的严重程度的疗效。采用标准化疾病严重程度评估、血清补体溶血活性、血清细胞毒性、乙酰胆碱受体（AChR）抗体浓度、IgG亚类和神经肌肉接头处C9沉积来评估补体抑制对AChR抗体或纯化AChR免疫诱导的EAMG的影响。在被动转移EAMG中施用rEV 576限制了疾病严重程度，如100%存活率和低疾病严重程度评分所证明。在活动性EAMG中，患有重度和轻度EAMG的大鼠免于疾病恶化，并且体重减轻有限。治疗期间，重度和轻度EAMG患者的血清补体活性（CH 50）降低至检测不到的水平，神经肌肉接头处的C9沉积减少。用rEV 576治疗导致来自重度和轻度EAMG大鼠的血清毒性降低。总AChR IgG和IgG2a抗体的水平相似，但出乎意料的是，补体固定IgG1抗体的浓度在一组rEV 576处理的动物中较低，表明rEV 576对细胞免疫的影响。抑制补体显着减少两种模型的EAMG的弱点。C5抑制可证明在人重症肌无力中具有显著的治疗价值。
Complement mediated injury of the neuromuscular junction is considered a primary disease mechanism in human myasthenia gravis and animal models of experimentally acquired myasthenia gravis (EAMG). We utilized active and passive models of EAMG to investigate the efficacy of a novel C5 complement inhibitor rEV576, recombinantly produced protein derived from tick saliva, in moderating disease severity. Standardized disease severity assessment, serum complement hemolytic activity, serum cytotoxicity, acetylcholine receptor (AChR) antibody concentration, IgG subclassification, and C9 deposition at the neuromuscular junction were used to assess the effect of complement inhibition on EAMG induced by administration of AChR antibody or immunization with purified AChR. Administration of rEV576 in passive transfer EAMG limited disease severity as evidenced by 100% survival rate and a low disease severity score. In active EAMG, rats with severe and mild EAMG were protected from worsening of disease and had limited weight loss. Serum complement activity (CH50) in severe and mild EAMG was reduced to undetectable levels during treatment, and C9 deposition at the neuromuscular junction was reduced. Treatment with rEV576 resulted in reduction of toxicity of serum from severe and mild EAMG rats. Levels of total AChR IgG, and IgG2a antibodies were similar, but unexpectedly, the concentration of complement fixing IgG1 antibodies was lower in a group of rEV576-treated animals, suggesting an effect of rEV576 on cellular immunity. Inhibition of complement significantly reduced weakness in two models of EAMG. C5 inhibition could prove to be of significant therapeutic value in human myasthenia gravis.
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DOI：
10.1073/pnas.80.13.4089
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
GOMEZ, CM;RICHMAN, DP
通讯作者：
RICHMAN, DP
影响因子：
56.9
作者：
KAO, I;DRACHMAN, DB
通讯作者：
DRACHMAN, DB
影响因子：
4.8
作者：
Hepburn, Natalie J.;Williams, Anwen S.;Harris, Claire L.
通讯作者：
Harris, Claire L.
DOI：
10.1111/j.1749-6632.1987.tb51301.x
发表时间：
1987-08-29
影响因子：
5.2
作者：
ENGEL, AG;ARAHATA, K
通讯作者：
ARAHATA, K
影响因子：
3.4
作者：
LINDSTROM, J;EINARSON, B
通讯作者：
EINARSON, B