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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：
10928530
负责人：
Steven Holland
金额：
$ 28.59万
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/10928530
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 Flow Cytometry Granulocyte-Macrophage Colony-Stimulating Factor IL17 gene Image Immunologic Deficiency Syndromes Immunologics Infection Infusion procedures Interferon Type II Intravenous infusion procedures Laboratories Mediator Methods Monoclonal Antibody CD20 Mucocutaneous Candidiasis Myasthenia Gravis 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 conventional therapy cytokine follow-up inflammatory marker insight non-tuberculous mycobacterial infection open label participant enrollment 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。我们将治疗患者并收集他们的血液并评估受疾病影响的区域，例如抗 IFNg 自身抗体相关的深部感染的成像、抗 IL-17 自身抗体相关的念珠菌病的内窥镜检查、GM-CSF 自身抗体相关的肺泡蛋白沉积症的支气管镜检查和/或 CT 成像。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。

项目成果

期刊论文数量（18）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Distinct Functions of Autoantibodies Against Interferon in Systemic Lupus Erythematosus: A Comprehensive Analysis of Anticytokine Autoantibodies in Common Rheumatic Diseases.

DOI：
10.1002/art.39607
发表时间：
2016-07
期刊：
Arthritis & rheumatology (Hoboken, N.J.)
影响因子：
0
作者：
Gupta S;Tatouli IP;Rosen LB;Hasni S;Alevizos I;Manna ZG;Rivera J;Jiang C;Siegel RM;Holland SM;Moutsopoulos HM;Browne SK
通讯作者：
Browne SK

A genetic perspective on granulomatous diseases with an emphasis on mycobacterial infections.

对肉芽肿性疾病的遗传观点，重点是分枝杆菌感染。