Control of immediate hypersensitivity responses in parasitic and other diseases

控制寄生虫病和其他疾病的速发型超敏反应

• 批准号: 7592227
• 负责人: Thomas B Nutman
• 金额: $ 60.86万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 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/7592227
• 关键词: Allergic; Antibodies; Antigens; Basophils; CD4 Positive T Lymphocytes; Chronic; Condition; Coupled; Disease; Elevation; Event; Genetic Transcription; Helminths; IL2RA gene; IgE; IgG4; Imatinib; Immediate hypersensitivity; Immune System Diseases; Immunoglobulin Switch Recombination; Infection; Inflammation; Institutes; Interleukin-10; Measurement; Measures; Mediating; Methods; Molecular; Parasitic infection; Patients; Physiological; Recruitment Activity; Regulation; Site; Source; Syndrome; Variant; eosinophil; monocyte; response; tool

Hypereosinophilic conditions have been studied extensively, and we have identified new markers that distinguish between several important variants of this syndrome. We have instituted new therapies (imatinib, anti-IL5) for the treatment of each of these variants. The interaction between helminth infeciton and allergic disease has been studied using epidemiological tools coupled with physiological measurements of allergic disease and immunological assessments. We have demonstrated that chronic helminth infection protects against allergic diseases. Studies done to date have demonstrated the CD4+ cells (and neither the monocytes nor the basophils) are the overwhelmingly major source of IL-10 in chronic filarial infection but they are not CD25+. We have also demonstrated that IgE mediated responses persist for decades even in the absence of antigen stimulation. We have developed quantitative methods for examination of germline transcription for each of the antibody isotypes and have begun to use these methods to examine the molecular events that occur when antigens induce specific switch recombination events. Also baseline IgE and IgG4 germline transcription profiles have been measured in patients with allergic and parasitic infections and associated elevations of IgE and IgG4.

高嗜酸性粒细胞增多症已经得到了广泛的研究，我们已经确定了区分这种综合征的几个重要变体的新标记物。我们已经制定了新的治疗方法(伊马替尼、抗IL5)来治疗这些变体。 利用流行病学工具，结合过敏性疾病的生理测量和免疫学评估，研究了蠕虫感染和过敏性疾病之间的相互作用。我们已经证明，慢性蠕虫感染可以预防过敏性疾病。到目前为止所做的研究表明，在慢性丝虫感染中，CD4+细胞(既不是单核细胞，也不是嗜碱性粒细胞)是绝大多数IL-10的主要来源，但它们不是CD25+。我们还证明，即使在没有抗原刺激的情况下，IgE介导的反应也会持续数十年。 我们已经开发了定量方法来检查每种抗体同种类型的生殖系转录，并开始使用这些方法来检查当抗原诱导特定开关重组事件时发生的分子事件。此外，还检测了过敏和寄生虫感染患者的基线IgE和IgG4生殖系转录谱，以及相关的IgE和IgG4水平升高。