Rituximab for Anticytokine Autoantibody-Associated Syndromes

利妥昔单抗治疗抗细胞因子自身抗体相关综合征

基本信息

批准号：
9356034
负责人：
Steven Holland
金额：
$ 17.46万
依托单位：
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9356034
关键词：
18 year old Affect Antibodies Antigens Autoantibodies Autoimmune Diseases B-Lymphocyte Subsets B-Lymphocytes Blood Bronchoscopy CD40 Ligand Candidiasis Clinical Data Disease Endoscopy Enrollment Flow Cytometry Granulocyte-Macrophage Colony-Stimulating Factor Human Image Infection Infusion procedures Interferon Type II Interleukin-17 Intravenous infusion procedures Laboratories Mediator of activation protein Methods Monoclonal Antibody CD20 Mucocutaneous Candidiasis Myasthenia Gravis Mycobacterium Infections Patients Pemphigus Vulgaris Pharmaceutical Preparations Process Production Progressive Disease Pulmonary Alveolar Proteinosis Quality of life Refractory Rheumatoid Arthritis Safety Surveys Syndrome Toxic effect Visit X-Ray Computed Tomography arm base chimeric antibody conventional therapy cytokine follow-up inflammatory marker insight open label phase I trial rituximab screening

项目摘要

Anti-cytokine autoantibodies have been shown to be an important mediator of certain serious diseases including immunodeificncy due to anti-IFNg autoantibodies and pulmonary alveolar proteinosis due to anti-GM-CSF autoantibodies. Some patients are refractory to optimized conventional therapy or have serious intolerance to standard approaches. We will be enrolling patients with anticytokine autoantibody syndromes who have have progressive disease despite optimized conventional treatment. We will treat patients and collect their blood and evaluate disease-affected regions however appropriate, i.e. imaging for anti-IFNg-autonantibody associated deep-seated infections, endoscopy for anti-IL-17-autoantibody-associated candidiasis, bronchoscopy or CT imaging for GM-CSF autoantibody associated pulmonary alveolar proteinosis. We will evaluate blood for changes in autoantibody levels using out luminex-based method for antibody screening, inflammatory markers using the clinical lab, and immunological parameters such as CD40 Ligand expression and B lymphocyte subsets using flow cytometry. We will also apherese patients prestudy and identify antigen-specific B cells (that recognize specific cytokines) by flow cytometry and ELIspot. We will also perform a quality of life survey pre and post study and clinically score disease activity to evaluate for evidence of efficacy. This study has support from Genetech who are providing drug as well as PK and PD data, and search for human anti-chimeric antibodies (HACAs).

抗周期动物自身抗体已被证明是某些严重疾病的重要介质，包括由于抗IFNG自身抗体和由于抗GM-CM-CSF自身抗体引起的抗IFNG自身抗体和肺肺泡蛋白质病。一些患者对优化常规治疗或对标准方法的严重不宽容是难治性的。尽管经过优化的常规治疗，但我们将招募患有疾病的抗细节自身抗体综合症患者。我们将治疗患者并收集他们的血液并评估受疾病影响的区域，即适当的，即与抗IFNG-氨基抗体相关的深座感染的成像，抗IL-17-17-自动抗体相关的念珠菌病的内窥镜检查，支气管镜检查，支气管镜检查，GM-CSF自身抗体蛋白酶蛋白酶蛋白酶均与GM-CSF自动抗体相关的CT成像。我们将使用基于Luminex的抗体筛查方法，使用临床实验室的炎症标记以及免疫学参数（例如CD40配体表达和B淋巴细胞亚群）使用基于Luminex的方法来评估自身抗体水平的变化。我们还将通过流式细胞仪和ELISPOT鉴定抗原特异性B细胞（识别特定细胞因子）的抗原特异性B细胞（识别特异性细胞因子）。我们还将进行研究前和研究后的生活质量调查，并在临床上对疾病活动进行评估以评估有效性的证据。这项研究得到了Genetech的支持，他们提供药物以及PK和PD数据，并搜索人类抗chimeric抗体（HACAS）。