Belimumab for Maintenance Therapy in Idiopathic Inflammatory Myositis

科学抽象 特发性炎症性肌炎（IIM）是一组异质性系统性疾病 以肌肉和其他器官的炎症为特征。不幸的是，有些病人 对目前可用的治疗方案难治。这导致了对小说的探索 治疗IIM。几条证据支持B细胞在IIM发病机制中的作用 并且因为发现高水平的B细胞存活细胞因子BAFF（B细胞活化因子 在受影响患者的血清和肌肉中，BAFF抑制被认为是相关的 治疗方法本提案的目的是描述 贝利木单抗，一种潜在的肌炎新治疗药物，在接受治疗的患者中， 多中心随机安慰剂对照临床试验。拟议的辅助研究 此处基于贝利木单抗将靶向幼稚B细胞和IFN驱动的 自身免疫性浆母细胞反应，并将直接或间接降低全身性 炎症、T细胞和单核细胞活化。技术将包括详细的表型分析 免疫细胞包括B细胞、T细胞和髓样细胞的分析，免疫球蛋白基因的分析 库，细胞因子的多重分析，药物对干扰素特征的影响， 选择的细胞亚群的转录谱。每名受试者将作为自己的对照， 将在整个试验期间定期采集样本。结果还将与 我们在SLE患者中进行的类似检测，以确定是否存在 两种疾病对贝利木单抗反应的差异。这些研究应该 贝利木单抗在肌肉炎症中作用机制的新发现， 可以帮助我们了解哪些肌炎患者可以从这种治疗中受益。

Scientific Abstract Idiopathic inflammatory myositis (IIM) is a heterogeneous group of systemic disorders characterized by inflammation in the muscle and other organs. Unfortunately some patients are refractory to currently available treatment options. This has led to the exploration of novel therapies for IIM. Several lines of evidence support a role for B cells in the pathogenesis of IIM and because high levels of the B cell survival cytokine BAFF (B cell activating factor) are found in the serum and muscle of affected patients, BAFF inhibition is considered a relevant therapeutic approach. The goal of this proposal is to characterize the mechanism of action of belimumab, a potential new therapeutic for myositis, in patients being treated in the setting of a funded multicenter randomized placebo controlled clinical trial. The ancillary studies proposed here are based on the hypotheses that belimumab will target naïve B cells and IFN driven autoimmune plasmablast responses and will, either directly or indirectly decrease systemic inflammation and T cell and monocyte activation. Technologies will include detailed phenotyping of immune cells including B cells, T cells and myeloid cells, analysis of immunoglobulin gene repertories, multiplex analyses of cytokines, effects of drug on the interferon signature and transcriptional profiling of selected cell subsets. Each subject will act as their own control and samples will be collected at intervals throughout the trial. Results will also be compared to those of similar assays we are performing in SLE patients to determine whether there are differences in responses to belimumab between the two diseases. These studies should shed new light on the mechanism of action of belimumab in the setting of muscle inflammation and may help us to understand which myositis patients may benefit from this therapy.