Therapeutic inhibition of the alternative complement pathway attenuates chronic EAE
Therapeutic inhibition of the alternative complement pathway attenuates chronic EAE
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DOI：
10.1016/j.molimm.2012.12.018
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发表时间：
2013-07-01
影响因子：
3.6
通讯作者：
Barnum, Scott R.
中科院分区：
文献类型：
--
作者：
Hu, Xianzhen;Holers, V. Michael;Barnum, Scott R.
我们实验室以前对补体突变小鼠的研究表明，替代途径是导致脱髓鞘疾病中补体介导的病理的主要激活途径。应用一种具有良好特性的针对小鼠B因子的抑制性单抗(MAb1379)，我们评价了抑制替代补体途径在实验性自身免疫性脑脊髓炎(EAE)中的治疗价值。在活动性EAE临床症状出现之前给小鼠注射B因子抗体对疾病的开始或急性期没有影响，但显著地减轻了疾病的慢性期，从而减少了抗体处理的小鼠的细胞渗透、炎症和脱髓鞘。即使在疾病发作后不久就终止了抗体给药，慢性期疾病的缓解也是长期的。在疾病发作之前或之后给予抗B因子抗体时，转移性EAE患者的慢性疾病也得到缓解。在使用MOG特异性脑源性T细胞转移的EAE中也观察到了相似的疾病缓解水平。这些研究证明了在慢性脱髓鞘疾病阶段抑制B因子的治疗潜力，在该阶段治疗选择有限。(C)2013爱思唯尔有限公司。保留所有权利。
Previous studies from our laboratory using complement-mutant mice demonstrated that the alternative pathway is the dominant activation pathway responsible for complement-mediated pathology in demyelinating disease. Using a well-characterized inhibitory monoclonal antibody (mAb 1379) directed against mouse factor B, we assessed the therapeutic value of inhibiting the alternative complement pathway in experimental autoimmune encephalomyelitis (EAE), the animal model for multiple sclerosis. Administration of anti-factor B antibody to mice prior to the onset of clinical signs of active EAE had no affect on the onset or acute phase of disease, but significantly attenuated the chronic phase of disease resulting in reduced cellular infiltration, inflammation and demyelination in antibody-treated mice. Attenuation of the chronic phase of disease was long lasting even though antibody administration was terminated shortly after disease onset. Chronic disease was also attenuated in transferred EAE when anti-factor B antibody was administered before or after disease onset. Similar levels of disease attenuation were observed in transferred EAE using MOG-specific encephalitogenic T cells. These studies demonstrate the therapeutic potential for inhibition of factor B in the chronic phase of demyelinating disease, where treatment options are limited. (C) 2013 Elsevier Ltd. All rights reserved.