Serological Biomarkers for Coccidioidomycosis
球孢子菌病的血清学生物标志物
基本信息
- 批准号:10625357
- 负责人:
- 金额:$ 37.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-06-07 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:Absenteeism at workActivities of Daily LivingAcuteAcute DiseaseAmericanAntibioticsAntibodiesAntibody ResponseAntibody titer measurementAntigensAreaArizonaBacterial PneumoniaBiological AssayBiological MarkersBlastomycosisBlood TestsBronchoalveolar LavageCaliforniaCategoriesChronicCloningCoccidioidesCoccidioidomycosisComplementCoughingDevelopmentDiagnosisDiagnosticDiagnostic testsDiseaseDrynessElderlyEnsureEnzyme ImmunoassayEnzyme-Linked Immunosorbent AssayEvaluationFungal SporesGrowthHealth PersonnelHistoplasmosisIllness DaysImmunoassayImmunocompetentImmunodiffusionImmunoglobulin GImmunoglobulin MIncidenceIndividualInfectionInhalationLaboratoriesLaboratory DiagnosisLearningLifeLungMeasuresMedicalMeningesMicro Array DataMorbidity - disease rateNucleic AcidsPatient MonitoringPatientsPerformancePhasePlasmidsPneumoniaPopulationPrecipitinsPreparationPrintingProceduresProductionPrognosisProtein ArrayProtein MicrochipsProteinsProteomePublishingReactionRecombinantsReportingReproducibilityReproduction sporesResourcesSamplingSchoolsSensitivity and SpecificitySerodiagnosesSerologySerology testSerumSick LeaveSiteSkinSoilSpecificitySputumStandardizationSurveysSymptomsSystemTestingTimeTranslatingTubeTuberculosisValidationViralViral Pneumoniaaccurate diagnosisaerosolizedantibody detectionantigen detectionboneclinical diagnosiscommunity acquired pneumoniacross reactivitydesert feverdetection assaydiagnosis standarddiagnostic strategyeconomic impactexperiencefabricationfollow-upfungusimmunoreactivityimprovedmortalitypreventresponseretireesample fixationscreeningseropositivesuccess
项目摘要
PROJECT SUMMARY
As of 2017, coccidioidomycosis (Cocci) also known as Valley Fever (VF) was designated a reportable
disease in 22 states (1). The majority of the cases in the US occur in southern Arizona and California where the
population is increasing with influx of naïve individuals, in particular, elderly retirees. Since Coccidioides sp, can
cause significant morbidity and mortality in fully immunocompetent hosts, this represents an important threat to
these regions where >10% percent of the US population resides, not including substantial tourist or part-time
resident populations in Arizona and California. Importantly, the reporting criteria require a positive laboratory
test for inclusion, yet ~50% of patients–who will eventually test positive–test negative while acutely ill (2). Testing
has low sensitivity and specificity leaving sick patients and their health care providers without an accurate
diagnosis. Thus, there is a profound need for better diagnostic approaches to properly identify Cocci patients to
ensure appropriate follow-up and therapy ensues.
Coccidioides spp. grow as mycelia in the desert soils and produce spores (arthroconidia) to survive during
times of adverse growth conditions. When this soil is disturbed, arthroconidia aerosolize and are inhaled to
initiate infection. Inside the host, the spores transform into spherules containing endospores which grow in the
lung. When spherules burst, endospores, are released and can each disseminate to form a new spherule.
Clinical diagnosis is difficult because patients’ symptoms resemble other bacterial and viral pneumonias.
Laboratory diagnosis often relies solely on serology, but ~50% of patients do not test positive while they are
acutely ill which results in inaccurate diagnosis an inappropriate treatment. We propose that it is time for a re-
evaluation of seroreactive coccidioidal antigens. For the past six decades, serologic diagnosis of
coccidioidomycosis has relied on IgM responses to tube precipitin (TP) and IgG responses to complement
fixation (CF) antigens. Since these antigens are primarily expressed in mycelia, not in spherules which is the
fungal form that grows in the host, it is not surprising that many patients are seronegative because they have not
yet generated antibodies to spherule antigens during acute pulmonary illness.
The GOAL of this proposal is to identify new coccidioidal antigens that react with acutely infected patient
sera. The objectives are to utilize the recently published Coccidioides spp. proteome to create a nucleic acid
programmable protein array (NAPPA) in which every coccidioidal protein is screened for reactivity with VF patient
sera. Our hypothesis is that this survey of the Coccidioides proteome will reveal new spherule-phase antigens
that are reactive with more patients, especially acutely ill patients who are seronegative for TP and/or CF
antigens. Once we identify a small panel of seroreactive antigens, they can be incorporated into existing antigen
preparations or a separate reliable, consistent, accurate test that will increase the number of positive diagnoses
in acutely ill patients with early disease.
项目概要
截至 2017 年,球孢子菌病 (Cocci) 也称为谷热 (VF) 被指定为需报告的疾病
22 个州患病 (1)。美国的大多数病例发生在亚利桑那州南部和加利福尼亚州,那里
随着天真的人,特别是老年退休人员的涌入,人口正在增加。由于球孢子菌 sp,可以
在完全免疫功能正常的宿主中引起显着的发病率和死亡率,这对
这些地区居住着超过 10% 的美国人口,不包括大量游客或兼职人员
亚利桑那州和加利福尼亚州的常住人口。重要的是,报告标准需要阳性实验室
测试是否包含在内,但约 50% 的患者(最终测试呈阳性)在病情严重时测试呈阴性 (2)。测试
敏感性和特异性较低,使患病患者及其医疗保健提供者无法获得准确的信息
诊断。因此,迫切需要更好的诊断方法来正确识别球菌患者
确保进行适当的随访和治疗。
球孢子菌属在沙漠土壤中作为菌丝体生长并产生孢子(节孢子)以在
不利生长条件的时期。当土壤受到干扰时,节孢子就会雾化并被吸入
引发感染。在宿主体内,孢子转化为含有内生孢子的小球,内生孢子在宿主体内生长。
肺。当小球破裂时,内生孢子被释放,并且可以各自散布形成新的小球。
临床诊断很困难,因为患者的症状类似于其他细菌性和病毒性肺炎。
实验室诊断通常仅依赖于血清学检测,但约 50% 的患者在检测时并未检测出阳性
病情严重,导致诊断不准确、治疗不当。我们建议现在是重新考虑的时候了
血清反应性球孢子抗原的评估。在过去的六十年里,血清学诊断
球孢子菌病依赖于对管沉淀素 (TP) 的 IgM 反应和对补体的 IgG 反应
固定(CF)抗原。由于这些抗原主要在菌丝体中表达,而不是在小球中表达,这是
由于真菌形式在宿主体内生长,因此许多患者呈血清阴性也就不足为奇了,因为他们没有
然而在急性肺部疾病期间产生了针对小球抗原的抗体。
该提案的目标是鉴定与急性感染患者发生反应的新球孢子抗原
血清。目标是利用最近发表的球孢子菌属。蛋白质组创建核酸
可编程蛋白质阵列 (NAPPA),其中筛选每种球孢子蛋白与 VF 患者的反应性
血清。我们的假设是,对球孢子菌蛋白质组的调查将揭示新的小球相抗原
对更多患者有反应,尤其是 TP 和/或 CF 血清阴性的急性患者
抗原。一旦我们鉴定出一小部分血清反应性抗原,就可以将它们纳入现有抗原中
准备工作或单独的可靠、一致、准确的测试将增加阳性诊断的数量
患有早期疾病的急性患者。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Clinical Laboratory Utility of a Humanized Antibody in Commercially Available Enzyme Immunoassays for Coccidioidomycosis.
- DOI:10.1128/spectrum.02573-22
- 发表时间:2022-10-26
- 期刊:
- 影响因子:3.7
- 作者:
- 通讯作者:
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DOUGLAS F. LAKE其他文献
DOUGLAS F. LAKE的其他文献
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{{ truncateString('DOUGLAS F. LAKE', 18)}}的其他基金
Serological Biomarkers for Coccidioidomycosis
球孢子菌病的血清学生物标志物
- 批准号:
10296008 - 财政年份:2021
- 资助金额:
$ 37.93万 - 项目类别:
Serological Biomarkers for Coccidioidomycosis
球孢子菌病的血清学生物标志物
- 批准号:
10418810 - 财政年份:2021
- 资助金额:
$ 37.93万 - 项目类别:
Engineered/Proteolytic Antibodies Specific/HIV-1 gp120
工程化/蛋白水解抗体特异性/HIV-1 gp120
- 批准号:
7294568 - 财政年份:2004
- 资助金额:
$ 37.93万 - 项目类别:
Engineered/Proteolytic Antibodies Specific/HIV-1 gp120
工程化/蛋白水解抗体特异性/HIV-1 gp120
- 批准号:
6798857 - 财政年份:2004
- 资助金额:
$ 37.93万 - 项目类别:
Validation of Coccidiodes Target Antigens for Immunotherapy
用于免疫治疗的球孢子菌靶抗原的验证
- 批准号:
6841448 - 财政年份:2004
- 资助金额:
$ 37.93万 - 项目类别:
Engineered/Proteolytic Antibodies Specific/HIV-1 gp120
工程化/蛋白水解抗体特异性/HIV-1 gp120
- 批准号:
6952658 - 财政年份:2004
- 资助金额:
$ 37.93万 - 项目类别:
Custon Designing Peptides for Cancer Immunotherapy
Custon 设计用于癌症免疫治疗的肽
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6874546 - 财政年份:2002
- 资助金额:
$ 37.93万 - 项目类别:
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