FUNGAL PROTEIN/GLYCOPROTEIN EXPRESSION IN TINEA CAPITIS

在世界范围内，头癣在儿童中仍然是一种持续和高度感染的疾病，任何时候都有多达十分之一的儿童表现出活跃的感染或作为真菌的携带者。1999年，在申请机构，我们每天治疗4.5名儿童。虽然头癣不危及生命，但它是一个主要的儿科健康问题，原因有几个：1)致病微生物是传染性的和非机会性的，2)感染对需要几个月到几年的系统抗真菌治疗的局部治疗没有足够的反应，3)对感染外观和传播的担忧导致儿童被排除在学术和社会活动之外，4)由于感染而患上永久性脱发的儿童存在心理问题。此外，诊所就诊、药物失效、不良事件、药物相互作用、不遵守规定、药物获取和监测费用以及相关发病率造成的医疗保健系统费用是儿科医学中的一个突出问题。尽管头癣早在一个多世纪前就已被描述，但感染率仍在继续增长，对这种疾病的发病机制所涉及的因素仍知之甚少。例如，目前尚不清楚为什么单一种类的真菌能够导致截然不同的临床表现，包括无症状携带者状态、慢性非炎症性疾病状态和急性严重炎症性疾病状态。宿主和真菌因素很可能都参与了复杂的相互作用，定义了人类宿主中的疾病进展。我们假设，抗原蛋白酶表达和免疫抑制糖蛋白产生之间的平衡中的菌株特异性差异决定了不同头癣儿童之间的反应差异。本研究旨在确定菌株特异性差异是否存在于(1)释放的真菌蛋白酶的类型，(2)真菌蛋白酶活性的程度和(3)从炎症性和非炎症性疾病的真菌分离株产生的真菌糖蛋白的类型。确定真菌蛋白/糖蛋白表达与临床疾病严重程度之间的相关性将更清楚地确定这些因素在疾病发病机制中的作用。这些真菌成分的成功表征是开发针对真菌中间代谢关键步骤的潜在治疗的第一步，对于分离足以激发免疫反应的真菌表位至关重要，该表位随后可以作为开发足以预防感染的疫苗的基础。

Worldwide, tinea capitis remains a persistent and highly infection in children with as many as 1 in 10 children at any ne time demonstrating active infection or serving as carriers of the fungus. At the applicant institution we treated 4.5 children per day in 1999. Although tinea capitis is not life threatening, it is a major pediatric health concern for a number of reasons: 1) the causative organisms are communicable and non- opportunistic, 2) the infection does not adequately respond to topical therapy requiring systemic antifungal treatment for months to years, 3) concerns regarding appearance and spread of infection lead to the exclusion of children from participation in academic and social activities and 4) psychological concerns surround those children who develop permanent alopecia as a result of infection. Moreover, the cost of health care systems from clinic visits, drug failure, adverse events, drug interactions, non-compliance, drug acquisition and monitoring costs and associated morbidity present an overwhelming problem in pediatric medicine. Despite the fact that tinea capitis was described over a century ago, the rate of infection continues to grow and little remains known regarding the factors involved in the pathogenesis of this disease. For example, it is unclear why a single species of fungus is capable of resulting in vastly divergent clinical presentations including an asymptomatic carrier state, a chronic non-inflammatory disease state and an acute severely-inflammatory disease state. It is likely that both host and fungal factors are involved in a complex interaction that defines disease progression in the human host. We hypothesize that strain- specific variability in the balance between antigenic protease expression and immunoinhibitory glycoprotein production dictates the variability in the response seen between different children with tinea capitis. This study is designed to determine whether strain specific differences exist in (1) the type of fungal proteases liberated, (2) the extent of fungal proteases activity and (3) the type of fungal glycoproteins produced for fungal isolates collected from children with inflammatory and non-inflammatory disease. Identification of a correlation between fungal protein/glycoprotein expression and the severity of clinical disease will more clearly define the role of these factors in disease pathogenesis. Successful characterization of these fungal elements is the first step toward developing potential treatment that targets critical steps in fungal intermediary metabolism and is critical for the isolation of fungal epitopes sufficient to evoke an immune response that can subsequently serve as the basis for the development of a vaccine sufficient to prevent infection.