Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis.
Memory B Cells are Major Targets for Effective Immunotherapy in Relapsing Multiple Sclerosis.
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DOI：
10.1016/j.ebiom.2017.01.042
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发表时间：
2017-02
期刊：
影响因子：
11.1
通讯作者：
Schmierer K
中科院分区：
文献类型：
--
作者：
Baker D;Marta M;Pryce G;Giovannoni G;Schmierer K
虽然多发性硬化症（MS）被认为是一种CD 4，Th 17介导的自身免疫性疾病，但支持性证据可能是间接的，通常基于动物研究，并受到CD 4消耗抗体控制复发MS的感知失败的质疑。β-干扰素、醋酸格拉替雷、细胞生长抑制剂、富马酸二甲酯、芬戈莫德、克拉屈滨、达克珠单抗、利妥昔单抗/ocrelizumab在物理上，或在那他珠单抗的情况下在功能上，也耗尽了CD 19+、CD 27+记忆B细胞。在CD 52和CD 20消耗后，这种消耗是实质性的和长期的，并且两者也诱导MS的长期抑制，治疗周期很少，表明诱导治疗活性。重要的是，记忆B细胞通过已知使MS恶化的B细胞活化因子（atacicept）和肿瘤坏死因子（英夫利昔单抗）阻断而增强。这产生了以记忆B细胞为中心的统一概念，其与MS的治疗、组织病理学和病因学方面一致。记忆B细胞活性与MS的病因学、病理学和治疗一致，被认为是T细胞介导的。记忆B细胞的缺失发生在所有有效的MS治疗中，并且在高效治疗中更为显著。使MS恶化的药物也可以增加记忆B细胞的产生。
Although multiple sclerosis (MS) is considered to be a CD4, Th17-mediated autoimmune disease, supportive evidence is perhaps circumstantial, often based on animal studies, and is questioned by the perceived failure of CD4-depleting antibodies to control relapsing MS. Therefore, it was interestingly to find that current MS-treatments, believed to act via T cell inhibition, including: beta-interferons, glatiramer acetate, cytostatic agents, dimethyl fumarate, fingolimod, cladribine, daclizumab, rituximab/ocrelizumab physically, or functionally in the case of natalizumab, also depleted CD19 +, CD27 + memory B cells. This depletion was substantial and long-term following CD52 and CD20-depletion, and both also induced long-term inhibition of MS with few treatment cycles, indicating induction-therapy activity. Importantly, memory B cells were augmented by B cell activating factor (atacicept) and tumor necrosis factor (infliximab) blockade that are known to worsen MS. This creates a unifying concept centered on memory B cells that is consistent with therapeutic, histopathological and etiological aspects of MS. Memory B cells activity is consistent with the etiology, pathology and therapy of MS, thought to be T cell-mediated. Deletion of memory B cells occurs with all effective MS treatments and is more marked with high-efficacy treatments. Drugs that worsen MS, can also increase memory B cell production.