Novel mechanisms of pathogenesis in idiopathic vaginitis

 描述(由申请人提供)：特发性阴道炎每年向医疗保健提供者就诊的人数高达200万人次。这种综合征的特征是阴道瘙痒、灼热、分泌物和不适，不是由酵母、细菌性阴道病或滴虫病引起的。我们建议的研究将集中在两个潜在的疾病机制：(1)新的阴道微生物(细菌或真菌)或(2)宿主粘膜免疫激活。虽然这是一种描述良好的临床表型，令患者和临床医生都感到沮丧，但潜在的病理生理学尚未得到评估。我们将使用深度测序来确定患有特发性阴道炎的妇女阴道中存在的细菌和真菌群落，并将这些群落与健康妇女进行比较，以确定是否有与这些症状相关的微生物特征。我们还将评估特发性阴道炎是对正常阴道微生物群的非典型免疫反应的假说，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激活情况，特别是评估炎症是否与对正常微生物区系的特应性Th2型反应有关，而与细菌抗原引起的先天免疫激活有关。阴道炎症状的自我治疗与超过5亿美元的非处方药销售有关。患有特发性阴道炎的女性会经历严重的心理困扰、性功能障碍和抑郁。确定目标病原体或免疫途径将对特发性阴道炎的医疗管理做出重大贡献，有可能缓解与缺乏诊断或治疗选择有关的重大痛苦，并 减少这种情况下多次重复就诊对医疗保健系统的负担。

 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.