Biomarker Identification, Viral Susceptibility and Management in S. aureus Colonized AD Patients

金黄色葡萄球菌定植 AD 患者的生物标志物鉴定、病毒敏感性和管理

基本信息

批准号：
10617702
负责人：
Lisa Ann Beck
金额：
$ 46.2万
依托单位：
UNIVERSITY OF ROCHESTER
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：
2020-04-06 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10617702
关键词：
Acne Affect Applications Grants Atopic Dermatitis Bacteria Biological Biological Markers Biology Cells Child Circulation Clinical Coupled Data Eczema Herpeticum Eczema Vaccinatum Enrollment Epithelium Experimental Designs Exposure to Fatality rate Functional disorder Genome Growth Human Immune Targeting Immunity Individual Infectious Skin Diseases Inflammatory Measures Mediating Microbe Pathogenesis Patients Phenotype Play Predisposition Production Publications Registries Ribosomal RNA Role Serum Severities Severity of illness Simplexvirus Site Skin Skin colonization Smallpox Smallpox Vaccine Staphylococcus aureus Surface Systemic Therapy Testing Vaccination Vaccinia virus Viral Virulence Factors Virulent Virus Diseases biomarker identification biomarker panel clinical predictors commensal bacteria enhancing factor experience gene product microbiome pathogen permissiveness prospective recruit response skin barrier skin disorder skin microbiome skin microbiota systemic inflammatory response treatment response

项目摘要

Project Summary/Abstract Staphylococcus aureus (S. aureus) has been strongly implicated as a causal factor in pathogenesis of atopic dermatitis (AD) since the 1970s, and is further supported by publications demonstrating S. aureus skin colonization precedes AD onset. ADRN studies found that 50% of AD subjects are colonized and this AD phenotype is associated with greater epidermal barrier dysfunction, type 2 immunity, disease severity and remarkable alterations in the skin microbiome (increased S. aureus relative abundance and reduced abundance of the commensal bacteria, Cutibacterium acnes (C. acnes). Additionally, S. aureus-colonized AD subjects are more likely to develop a severe viral condition, called eczema herpeticum. An even more serious condition is eczema vaccinatum, caused by exposure to vaccinia virus (smallpox vaccination), which has a fatality rate as high as 30%. In an effort to explain this, we found discovered that epidermal exposure to a highly virulent S. aureus strain (USA300), commonly found on AD subjects, markedly enhances its susceptibility to vaccinia virus. Collectively, these observations support our hypothesis that S. aureus may be a key driver of disease severity and response to systemic treatments (Aim 1) as well as serious viral complications (Aim 2). Determining what role C. acnes, the most abundant commensal skin bacteria, plays in suppressing S. aureus will be the focus of studies outlined in Aim 3. These studies will leverage the wealth of deeply-phenotyped AD subjects and their biospecimens from previous ADRN studies (ADRN02-Registry, ADRN06-ADEH and ADRN09-Dupilumab) and those enrolled into URMCs Longitudinal ‘Real-World’ AD Study. The Aims demonstrate how the focus is first on the systemic features of S. aureus colonization (e.g. macro level; Aim 1) and moves to the “epidermal (host) – microbiome” interaction (Aim 2) and ultimately to the microbe-microbe interaction at the skin surface (e.g. micro level; Aim 3).

项目摘要/摘要金黄色葡萄球菌（金黄色葡萄球菌）已被极大地牵涉到特应特应特征性发病机理的因素皮肤炎（AD）以来自1970年代起，并得到了表明金黄色葡萄球菌皮肤的出版物的进一步支持殖民化先于AD发作。 ADRN研究发现，50％的AD受试者被定殖，此AD 表型与更大的表皮屏障功能障碍，第2型免疫培训，疾病严重程度和皮肤微生物组的显着改变（金黄色葡萄球菌相对丰度增加并减少共生细菌的丰度，cutibacterium痤疮（C.痤疮）。另外，金黄色葡萄球菌化 AD受试者更有可能发展出严重的病毒状况，称为湿疹。更多严重的病态是湿疹疫苗，由接触疫苗病毒（天花疫苗）引起的湿疹疫苗。死亡率高达30％。为了解释这一点，我们发现表皮暴露对于高度毒的金黄色葡萄球菌菌株（USA300），通常在AD受试者上发现，显着增强了其易感性病毒的敏感性。总的来说，这些观察结果支持我们的假设，即金黄色葡萄球菌可能是疾病严重程度的主要驱动力和对全身治疗的反应（AIM 1）以及严重的病毒并发症（目标2）。确定角色C.痤疮的角色，最丰富的共生皮肤细菌发挥作用在抑制金黄色葡萄球菌时，将成为AIM 3中概述的研究重点。这些研究将利用财富来自先前ADRN研究的深层广告主体及其生物测量（ADRN02-Registry， ADRN06-ADEH和ADRN09-DUPILUMAB）以及进入URMCS纵向“现实世界”广告的AD 学习。目的表明，焦点是如何首先放在金黄色葡萄球菌定植的系统特征上（例如宏观水平；目标1）并转到“表皮（宿主） - 微生物组”互动（AIM 2），最终到达皮肤表面的微生物微生物相互作用（例如微水平；目标3）。