Development &validationof a panel of antibodies for the diagnosis of sarcoidosis

发展

基本信息

批准号：
8392229
负责人：
Lobelia Samavati
金额：
$ 21.71万
依托单位：
WAYNE STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-01-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8392229
关键词：
Affect African American Antibodies Antigens Antinuclear Antibodies Autoantibodies Bacterial Antigens Bacteriophage T7 Bacteriophages Clinical Collection Crohn&apos s disease Cutaneous Databases Development Diagnosis Diagnostic Disease Drug Targeting Etiology Eye Future Granuloma Granulomatous Health Humoral Immunities Hypergammaglobulinemia Immune System Diseases Immune response Immunity Immunoglobulin G Immunotherapy Incidence Individual Inflammation Inflammatory Lung Lung diseases Lupus Erythematosus Lymph Node Tissue Mediastinal lymph node group Messenger RNA Molecular Target Neuraxis Organ Pathogenesis Pathway interactions Patients Pulmonary Sarcoidosis Recording of previous events Rheumatoid Arthritis Rheumatoid Factor Role Sarcoidosis Sensitivity and Specificity Sequence Analysis Sequence Homology Serum Skin Societies Testing Tissues Tuberculosis Viral Antigens Woman anergy base cDNA Library case control human disease immune function instrument lymph nodes men tool

项目摘要

DESCRIPTION (provided by applicant): This proposal will test the hypothesis that immunity has a prominent role in the pathogenesis of sarcoidosis, as suggested by abnormalities of the immune function and by the presence of antibodies, including rheumatoid factors and antinuclear antibodies found in this disorder. In addition, sarcoidosis coexists with other systemic inflammatory diseases, and patients frequently show cutaneous anergy and hypergammaglobulinemia. We propose to develop a panel of antibodies/autoantibodies with high sensitivity and specificity to identify patients with sarcoidosis and help to distinguish these patients from controls and individuals with other pulmonary diseases. For this purpose we will construct a T7 phage cDNA library of potential sarcoidosis antigens using mRNA isolated from affected lymph node tissue of patients with sarcoidosis. This cDNA library will be immunoscreened with sera from patients with sarcoidosis containing high titer IgG antibodies and the cloned colonies will be used to construct an antigen microarray that will be hybridized with sera from cases with lung sarcoidosis and controls. Control sera will be obtained from patients with sero-positive rheumatoid arthritis and from patients with a history of tuberculosis. Sequence analyses of informative phage inserts recognized as antigens by sarcoidosis patient sera may identify antigens associated with the etiopathogenesis of sarcoidosis. The autoantibody classifier will be validated with independently obtained collections of sera from cases and controls. In the future, this approach may identify molecular targets useful for the treatment of sarcoidosis.

描述（由申请人提供）：该提案将检验以下假设：由于免疫功能的异常和存在抗体，包括类风湿因子和抗核抗体在这种疾病中发现的抗体，因此在结节病的发病机理中具有重要作用。此外，结节病与其他全身性炎症性疾病并存，患者经常表现出皮肤性厌食和高肿瘤性疾病。我们建议开发一组具有高灵敏度和特异性的抗体/自身抗体，以鉴定患有结节病的患者，并有助于将这些患者与其他肺部疾病的对照组和患者区分开。为此，我们将使用从影响的结节病患者的淋巴结组织中分离的mRNA构建一个潜在结节抗原的T7噬菌体cDNA文库。该cDNA文库将用含有高滴度IgG抗体的结节病患者的血清进行免疫镜，并将使用克隆的菌落来构建一种抗原微阵列，该抗原微阵列将与肺部结节病和对照病例的血清杂交一起杂交。对照血清将获得血清阳性类风湿关节炎和结核病史的患者。通过结节病患者识别为抗原的信息噬菌体插入的序列分析可能会鉴定与结节病的疗法发生相关的抗原。自动抗体分类器将通过从病例和对照组中独立获得的血清收集来验证。将来，这种方法可以鉴定出可用于治疗结节病的分子靶标。