Regulatory T cell function in predicting Valley fever outcomes

调节性 T 细胞功能预测谷热结果

基本信息

批准号：
9979119
负责人：
Katrina K Hoyer
金额：
$ 23.55万
依托单位：
UNIVERSITY OF CALIFORNIA, MERCED
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-03-09 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9979119
关键词：
Activities of Daily Living Acute Adult Aftercare Age Algorithms Antibiotic Therapy Antifungal Agents Area Arizona Bacterial Infections Biological Factors Biological Markers Blood California Case Study Cell physiology Cells Cessation of life Child Childhood Chronic Chronic Disease Clinic Clinical Coccidioides Coccidioides immitis Coccidioides posadasii Coccidioidomycosis Contracts Data Data Set Detection Diagnosis Diagnostic Disease Disease Outcome Dust Evaluation Frequencies Health Immune Immune response Immunity Immunologic Factors Immunologic Markers Impaired health Incidence Infection Inhalation Knowledge Lung nodule Measurement Methods Mexico Modeling Monitor Mus Outcome Patient Care Patients Pharmaceutical Preparations Phenotype Population Predictive Factor Recurrent disease Regulatory T-Lymphocyte Relapse Resolution Severities Severity of illness Soil South America Southwestern United States Symptoms Testing Time Translational Research Travel Vaccines Washington Weather acute infection adaptive immune response aggressive therapy base chronic infection desert fever eosinophil experience flu fungus improved neutrophil novel older patient pathogenic fungus pediatric patients peripheral blood prediction algorithm predictive modeling predictive test prevent research study response side effect tool transmission process

项目摘要

PROJECT SUMMARY Coccidioidomycosis, known as Valley fever, is caused by the fungal pathogen (Coccidioides) endemic to the San Joaquin Valley in California, Arizona, northern Mexico and arid areas of South America. Incidence in California is on the rise, and there is evidence indicating that the disease can be found in non-endemic regions including Washington State. Population expansion, travel, detection and/or weather changes appear to be contributing to an expanding endemic region. The health impacts of Valley fever infection can range from superficial to lethal. For the 60% of people who are infected, but do not display symptoms of Valley fever, the impact of the disease is likely to be minimal. For the 40% of symptomatic patients, most will display symptoms similar to the flu and the condition will resolve without treatment. Nevertheless, these patients can experience significantly impaired health for a lengthy period of time. For 1% of the patients, Valley fever results in a severe or prolonged clinical illness with dramatic health impacts, including chronic pulmonary nodules or cavities, with the potential for misdiagnosis, and even death. Disease is often misdiagnosed as a bacterial infection, often resulting in several rounds of antibiotic treatments before a correct diagnosis. The health impacts of Valley fever infection thus vary dramatically, and little is known about the biological factors that influence the severity of symptoms and health complications experienced following infection. Although the details are still unclear, cellular immune responses have long been shown to be critical for effective immunity to Coccidioides infection. We recently determined that the inability to resolve Coccidioides infection may be a result of elevated regulatory T cell frequency and functional capacity, and that regulatory T cell frequency may predict patient disease outcome at diagnosis. We propose to: 1) define the phenotype and function of regulatory T cells in Coccidioides infected patients during early disease, and 2) to define a biomarker algorithm that can be used at diagnosis for calibrating treatment aggressiveness for those patients most likely to develop chronic cocciodiomycosis. The successful completion of this project will provide diagnostic tools to identify patients earlier in their disease course for more aggressive treatment and closer monitoring for relapse after treatment, and will better define the immune mechanisms underlying chronic cocciodiomycosis.

项目概要球孢子菌病，也称为谷热，是由当地流行的真菌病原体（球孢子菌）引起的。圣华金河谷位于加利福尼亚州、亚利桑那州、墨西哥北部和南美洲的干旱地区。发病率加州呈上升趋势，有证据表明该病可在非流行地区发现包括华盛顿州。人口扩张、旅行、探测和/或天气变化似乎是有助于扩大流行区域。谷热感染对健康的影响范围包括肤浅到致命。对于 60% 的感染者但没有表现出谷热症状的人来说，该疾病的影响可能很小。对于40%的有症状患者来说，大多数都会出现症状与流感类似，无需治疗即可痊愈。然而，这些患者可能会经历健康状况在很长一段时间内受到严重损害。对于 1% 的患者来说，谷热会导致严重的症状或对健康产生严重影响的长期临床疾病，包括慢性肺结节或空洞，误诊甚至死亡的可能性。疾病经常被误诊为细菌感染，导致在正确诊断之前进行几轮抗生素治疗。 Valley 对健康的影响因此，发烧感染的情况差异很大，而对于影响严重程度的生物学因素知之甚少感染后出现的症状和健康并发症。尽管细节仍不清楚，但细胞免疫反应早已被证明对于对球孢子菌感染具有有效的免疫力。我们最近确定无法解决球孢子菌感染可能是调节性 T 细胞频率和功能能力升高的结果，并且调节性 T 细胞细胞频率可以预测诊断时患者的疾病结果。我们建议：1）定义表型和球孢子菌感染患者在疾病早期期间调节性 T 细胞的功能，以及 2) 定义可用于诊断的生物标志物算法，用于校准这些患者的治疗积极性最有可能发展为慢性球孢菌病。该项目的顺利完成将提供诊断工具可在病程早期识别患者，以便进行更积极的治疗和更密切的治疗监测治疗后复发，并将更好地确定慢性病背后的免疫机制球孢菌病。