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：
10274159
负责人：
Steven Holland
金额：
$ 21.55万
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/10274159
关键词：
18 year old Affect Antibodies Antigens Autoantibodies Autoimmune Diseases B-Lymphocyte Subsets B-Lymphocytes Blood Bronchoscopy CD40 Ligand Candidiasis Clinical Disease Endoscopy Enrollment Flow Cytometry Granulocyte-Macrophage Colony-Stimulating Factor Image Immunologic Deficiency Syndromes Immunologics 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 Pathogenicity Patients Pemphigus Vulgaris Process Production Progressive Disease Pulmonary Alveolar Proteinosis Quality of life Refractory Rheumatoid Arthritis Safety Surveys Syndrome Toxic effect Visit X-Ray Computed Tomography anti-CD20 arm base conventional therapy cytokine follow-up inflammatory marker insight non-tuberculosis mycobacteria 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 immunodeficiency 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 are enrolling patients with anticytokine autoantibody syndromes who 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-autoantibody associated deep-seated infections, endoscopy for anti-IL-17-autoantibody-associated candidiasis, bronchoscopy and/or CT imaging for GM-CSF autoantibody associated pulmonary alveolar proteinosis. We will evaluate blood for changes in autoantibody levels using our 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.

抗细胞因子自身抗体已被证明是某些严重疾病的重要介质，包括抗 IFNg 自身抗体引起的免疫缺陷和抗 GM-CSF 自身抗体引起的肺泡蛋白沉着症。一些患者对优化的常规治疗耐药或对标准方法严重不耐受。我们正在招募患有抗细胞因子自身抗体综合征的患者，尽管经过了优化的常规治疗，但这些患者的疾病仍在进展。我们将治疗患者并采集他们的血液，并以适当的方式评估受疾病影响的区域，即针对抗 IFNg 自身抗体相关的深部感染进行成像、针对抗 IL-17 自身抗体相关念珠菌病的内窥镜检查、支气管镜检查和/或 CT 成像用于 GM-CSF 自身抗体相关的肺泡蛋白沉积症。我们将使用基于 luminex 的抗体筛查方法评估血液中自身抗体水平的变化，使用临床实验室评估炎症标记物，并使用流式细胞术评估 CD40 配体表达和 B 淋巴细胞亚群等免疫学参数。我们还将通过流式细胞术和 ELIspot 预先研究和鉴定抗原特异性 B 细胞（识别特定细胞因子）。我们还将在研究前后进行生活质量调查，并对疾病活动进行临床评分，以评估疗效证据。