FUNGAL PROTEIN/GLYCOPROTEIN EXPRESSION IN TINEA CAPITIS

在世界范围内，头癣仍然是儿童中一种持续和高度感染的疾病，在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。虽然头癣不会危及生命，但由于以下几个原因，它是一个主要的儿科健康问题：1)致病微生物具有传染性和非机会性，2)感染对局部治疗没有足够的反应，需要数月至数年的全身抗真菌治疗，3)对感染的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)心理上的担忧围绕着那些因感染而发展为永久性脱发的儿童。此外，从门诊就诊、药物失效、不良事件、药物相互作用、不遵守、药物获取和监测成本以及相关发病率等方面产生的卫生保健系统成本，是儿科医学中一个压倒性的问题。尽管头癣早在一个多世纪以前就被描述过，但其感染率仍在持续增长，而且对这种疾病的发病机制所涉及的因素知之甚少。例如，目前尚不清楚为什么一种真菌能够导致截然不同的临床表现，包括无症状载体状态、慢性非炎症性疾病状态和急性严重炎症性疾病状态。很可能宿主和真菌因子都参与了一种复杂的相互作用，这种相互作用决定了人类宿主的疾病进展。我们假设，在抗原性蛋白酶表达和免疫抑制性糖蛋白产生之间的平衡中的菌株特异性变异性决定了不同儿童头癣反应的变异性。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)真菌蛋白酶的活性程度，以及(3)从患有炎症性疾病和非炎症性疾病的儿童中收集的真菌分离物产生的真菌糖蛋白的类型。鉴定真菌蛋白/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。成功表征这些真菌成分是开发潜在治疗方法的第一步，这些治疗方法针对真菌中间代谢的关键步骤，并且对于分离真菌表位至关重要，足以引起免疫反应，随后可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.