Mechanisms of Response and Relapse in Rituximab-treated Myositis Patients

利妥昔单抗治疗肌炎患者的缓解和复发机制

基本信息

项目摘要

DESCRIPTION (provided by applicant): Autoimmune (AI) inflammatory muscle diseases (myositis) include polymyositis (PM), adult dermatomyositis (DM) and juvenile dermatomyositis (JDM). These rare diseases cause significant morbidity and can lead to death. One of the more novel treatments for myositis as well as other autoimmune diseases is B cell depletion (BCD) therapy with a biologic agent, rituximab. We studied rituximab in a recently completed clinical trial in myositis termed the Rituximab in Myositis (RIM) Study. The RIM Study is the first and largest controlled clinical trial ever performed in AI inflammatory muscle disease. The mechanism(s) by which rituximab improves myositis and other AI diseases is unclear and this study proposes to determine rituximab's mechanism of action in myositis. By doing so, we will not only learn how BCD works in myositis, but also the mechanism by which it improves AI disease in general. The studies proposed in this application will be completed using specimens that were prospectively collected from the RIM cohort of 200 myositis patients; the RIM cohort included both adult and pediatric patients with myositis (PM, DM and JDM). In conjunction with the specimens collected, valuable clinical information was also obtained so that the laboratory results from the experiments that are performed can be correlated with accurate, prospectively collected clinical data to provide us with an unmatched dataset in myositis. The immune system is affected in all AI diseases and this study proposes to examine the three major arms of the immune system and how rituximab affects T cell, B cell and innate immune responses. In this way, this proposal will also determine the relevant abnormal immune mechanisms that mediate myositis. PUBLIC HEALTH RELEVANCE (provided by applicant): Inflammatory muscle diseases including polymyositis, adult dermatomyositis and juvenile dermatomyositis cause significant health problems and can lead to death. Recent studies indicate that rituximab is an effective therapy for myositis patients. This application will determine the mechanisms by which rituximab works using samples collected from myositis subjects treated with rituximab in the RIM study.
自身免疫性(AI)炎症性肌肉疾病(肌炎)包括多发性肌炎(PM)、成人皮肌炎(DM)和青少年皮肌炎(JDM)。这些罕见疾病的发病率很高,并可导致死亡。治疗肌炎和其他自身免疫性疾病的新方法之一是使用生物制剂利妥昔单抗治疗B细胞耗竭(BCD)。我们在最近完成的一项名为利妥昔单抗肌炎(RIM)研究的肌炎临床试验中研究了利妥昔单抗。RIM研究是迄今为止在AI炎症性肌肉疾病中进行的第一个也是最大的对照临床试验。利妥昔单抗改善肌炎和其他AI疾病的机制尚不清楚,本研究拟确定利妥昔单抗在肌炎中的作用机制。通过这样做,我们不仅将了解BCD如何在肌炎中起作用,而且还将了解它改善一般AI疾病的机制。本申请中提出的研究将使用从200名肌炎患者的RIM队列中前瞻性收集的标本来完成;RIM队列包括成人和儿童肌炎患者(PM, DM和JDM)。结合所收集的标本,还获得了有价值的临床信息,以便进行的实验的实验室结果可以与准确的、前瞻性收集的临床数据相关联,从而为我们提供肌炎的无与伦比的数据集。免疫系统在所有AI疾病中都受到影响,本研究拟研究免疫系统的三个主要分支,以及利妥昔单抗如何影响T细胞、B细胞和先天免疫反应。通过这种方式,本建议也将确定介导肌炎的相关异常免疫机制。

项目成果

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MARC C. LEVESQUE其他文献

MARC C. LEVESQUE的其他文献

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{{ truncateString('MARC C. LEVESQUE', 18)}}的其他基金

Mechanisms of Response and Relapse in Rituximab-treated Myositis Patients
利妥昔单抗治疗肌炎患者的缓解和复发机制
  • 批准号:
    8522158
  • 财政年份:
    2010
  • 资助金额:
    $ 32.11万
  • 项目类别:
Mechanisms of Response and Relapse in Rituximab-treated Myositis Patients
利妥昔单抗治疗肌炎患者的缓解和复发机制
  • 批准号:
    8318804
  • 财政年份:
    2010
  • 资助金额:
    $ 32.11万
  • 项目类别:
Mechanisms of Response and Relapse in Rituximab-treated Myositis Patients
利妥昔单抗治疗肌炎患者的缓解和复发机制
  • 批准号:
    8146973
  • 财政年份:
    2010
  • 资助金额:
    $ 32.11万
  • 项目类别:
Randomized observation study of biologic therapy for rheumatoid arthritis
类风湿性关节炎生物治疗的随机观察研究
  • 批准号:
    8040371
  • 财政年份:
    2010
  • 资助金额:
    $ 32.11万
  • 项目类别:
Randomized observation study of biologic therapy for rheumatoid arthritis
类风湿性关节炎生物治疗的随机观察研究
  • 批准号:
    7942942
  • 财政年份:
    2009
  • 资助金额:
    $ 32.11万
  • 项目类别:
Randomized observation study of biologic therapy for rheumatoid arthritis
类风湿性关节炎生物治疗的随机观察研究
  • 批准号:
    7856255
  • 财政年份:
    2009
  • 资助金额:
    $ 32.11万
  • 项目类别:
Prevention of Chronic Lymphocytic Leukemia (CLL)
预防慢性淋巴细胞白血病 (CLL)
  • 批准号:
    7490723
  • 财政年份:
    2007
  • 资助金额:
    $ 32.11万
  • 项目类别:
Prevention of Chronic Lymphocytic Leukemia (CLL)
预防慢性淋巴细胞白血病 (CLL)
  • 批准号:
    7263427
  • 财政年份:
    2007
  • 资助金额:
    $ 32.11万
  • 项目类别:
Human TNFa-Induced Pre-B Cell Bone Marrow Emigrants
人 TNFa 诱导的前 B 细胞骨髓移出
  • 批准号:
    7105129
  • 财政年份:
    2006
  • 资助金额:
    $ 32.11万
  • 项目类别:
Human TNFa-Induced Pre-B Cell Bone Marrow Emigrants
人 TNFa 诱导的前 B 细胞骨髓移出
  • 批准号:
    7268102
  • 财政年份:
    2006
  • 资助金额:
    $ 32.11万
  • 项目类别:

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Rates and Risk Factors for Hepatitis C Re-Infection or Late Relapse after Sustained Virologic Response to Treatment among HIV Co-Infected Canadians
合并感染艾滋病毒的加拿大人对治疗产生持续病毒学反应后丙型肝炎再次感染或晚期复发的比率和危险因素
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Chronic Alcohol, Stress Inflammatory Response and Relapse Risk
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