Intrathecal IgG synthesis: a resistant and valuable target for future multiple sclerosis treatments.
Intrathecal IgG synthesis: a resistant and valuable target for future multiple sclerosis treatments.
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DOI：
10.1155/2015/296184
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发表时间：
2015
影响因子：
2.5
通讯作者：
Bonnan M
中科院分区：
文献类型：
--
作者：
Bonnan M
鞘内IgG合成是多发性硬化（MS）的关键生物学特征。如果早期获得，它会随着时间的推移而持续。越来越多的证据表明，鞘内免疫球蛋白分泌细胞可能通过有毒免疫球蛋白的直接作用或通过局部分泌旁观者有毒产物而具有致病性。鞘内IgG合成依赖于CNS淋巴器官的存在，CNS淋巴器官在解剖学水平上与皮质软膜下病变密切相关，在临床水平上与进行性MS的损伤斜率密切相关。因此，靶向CNS淋巴病变可能是MS中有价值的新靶点，特别是在进行性阶段。由于鞘内IgG是这些淋巴病变的终产物，因此鞘内IgG合成可被视为这些炎性病变持续存在的特异性标志物。在这里，我们回顾了鞘内IgG合成的所有药物在MS中使用的效果。除了类固醇，所有这些治疗策略，包括利妥昔单抗，未能减少鞘内IgG合成，除了那他珠单抗的一个可疑的不完整的行动。因此，IgG合成是持续性鞘内炎症的一个强有力的标志物，其完全正常化应该是未来治疗策略的目标之一。
Intrathecal IgG synthesis is a key biological feature of multiple sclerosis (MS). When acquired early, it persists over time. A growing body of evidence suggests that intrathecal Ig-secreting cells may be pathogenic either by a direct action of toxic IgG or by locally secreting bystander toxic products. Intrathecal IgG synthesis depends on the presence of CNS lymphoid organs, which are strongly linked at anatomical level to cortical subpial lesions and at clinical level to the impairment slope in progressive MS. As a consequence, targeting CNS lymphoid lesions could be a valuable new target in MS, especially during the progressive phase. As intrathecal IgGs are end-products of these lymphoid lesions, intrathecal IgG synthesis may be considered as a specific marker of the persistence of these inflammatory lesions. Here we review the effect upon intrathecal IgG synthesis of all drugs ever used in MS. Except for steroids, all these therapeutic strategies, including rituximab, failed to decrease intrathecal IgG synthesis, with the exception of a questionable incomplete action of natalizumab. Thus, IgG synthesis is a robust marker of persistent intrathecal inflammation and its complete normalization should be one of the goals in future therapeutic strategies.