Novel mechanisms of pathogenesis in idiopathic vaginitis

特发性阴道炎发病机制的新机制

基本信息

批准号：
8969791
负责人：
Caroline M Mitchell
金额：
$ 28.06万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-07-15 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8969791
关键词：
Accounting Aerobic Allergic rhinitis Anti-Inflammatory Agents Anti-inflammatory Asthma Atopic Dermatitis Bacteria Bacterial Antigens Bacterial Vaginosis Burn injury Candida Categories Communities Cross-Sectional Studies Development Diagnosis Diagnostic Disease Distress Enzyme-Linked Immunosorbent Assay Epithelial Cells Erythema Etiology Evaluation Extrinsic asthma Flow Cytometry Functional disorder Gram&apos s stain Granulocyte-Macrophage Colony-Stimulating Factor Health Care Visit Health Personnel Healthcare Systems High-Throughput Nucleotide Sequencing IL18 gene IL2 gene IL4 gene IL5 gene IL6 gene IL8 gene IL9 gene IgE Immune Immune response Immunologics Inflammation Inflammatory Inflammatory Response Integration Host Factors Interferon Type II Interleukin-1 beta Interleukin-13 Leukocytes Measurement Measures Medical Mental Depression Microbe Molecular Mucosal Immune Responses Names Odors Pain Pathogenesis Pathway interactions Patients Pattern Pharmaceutical Preparations Phenotype Population Premenopause Pruritus Recurrence Research Ribosomal RNA Sales Sampling Sexual Dysfunction Stimulus Swab Symptoms Syndrome Testing Therapeutic Topical Antibiotic Trichomonas Trichomonas Infections Vagina Vaginal Itching Vaginitis Variant Visit Woman Yeasts base clinical Diagnosis clinical phenotype clinically significant cytokine deep sequencing eosinophil experience fungus immune activation irritation microbial microbial community microbial host neutrophil novel pathogen psychologic public health relevance rRNA Genes response routine Bacterial stain vaginal fluid

项目摘要

DESCRIPTION (provided by applicant): Idiopathic vaginitis accounts for up to 2 million visits to health care providers each year. This syndrome is characterized by vaginal itching, burning, discharge and discomfort not attributed to yeast, bacterial vaginosis or trichomoniasis. Our proposed research will focus on two potential mechanisms of disease: (1) novel vaginal microbes (bacterial or fungal) or (2) host mucosal immune activation. Although this is a well-described clinical phenotype that is frustrating for patients and clinicians alike, the underlying pathophysiology has not been evaluated. We will use deep sequencing to identify the bacterial and fungal communities present in the vagina of women with idiopathic vaginitis and will compare these with healthy women to determine whether there is a microbial signature associated with these symptoms. We will also evaluate the hypothesis that idiopathic vaginitis is an atypical immune response to otherwise normal vaginal microbiota, similar to atopic dermatitis or asthma. We will evaluate the mucosal immune activation profile in these women, specifically assessing whether inflammation is related to an atopic, Th2-type response to normal microbiota versus an innate immune activation due to bacterial antigens. Self-treatment of vaginitis symptoms is associated with over 500 million dollars in sales of over-the-counter medications. Women with idiopathic vaginitis experience significant psychologic distress, sexual dysfunction and depression. Identifying a target pathogen or immunologic pathway would make a significant contribution to the medical management of women with idiopathic vaginitis, with potential to relieve the significant distress associated with the lack of diagnostic or treatment options and to decrease the burden on the health care system related to multiple repeat visits for this condition.

描述（由申请提供）：每年对医疗保健提供者的特发性阴道最多访问。该综合征的特征是阴道瘙痒，燃烧，排出和不适，而不是酵母，阴道疾病或毛瘤病。我们提出的研究将重点介绍两种潜在的疾病机制：（1）新型的阴道微生物（细菌或真菌）或（2）宿主粘膜免疫激活。尽管这是一种描述的临床表型，这对患者和临床医生都令人沮丧，但尚未评估潜在的病理生理学。我们将使用深层测序来识别具有特发性阴道女性的阴道中存在的细菌和真菌群落，并将与健康的女性进行比较，以确定是否存在与这些符号相关的微生物签名。我们还将评估以下假设：特发性阴道是对正常阴道微生物群的非典型免疫反应，类似于特应性皮炎或哮喘。我们将评估这些女性的粘膜免疫反应率，特别评估炎症是否与特应性的，Th2型对正常微生物群的反应相对于细菌抗原引起的先天性免疫反应。阴道症状的自我治疗与超过5亿美元的非处方药销售有关。识别靶标的病原体或免疫途径的妇女将为患有特发性阴道的妇女的医疗管理做出重大贡献，并有可能减轻与缺乏诊断或治疗方案相关的重大困扰以及对减少与此情况多次重复访问有关的医疗保健系统的烧伤。