ERYTHEMA MULTIFORME; A CLINICAL PATHOGENETIC STUDY

我们以前的临床和病理调查红斑 多形性疱疹病毒（EM）已经证明，单纯疱疹病毒是 与EM密切相关，疱疹相关EM（HAEM）是 最常见的EM形式。 我们进一步观察到 复发性EM几乎总是与HSV有关。 皮肤中 从EM的活动性病变获得，我们检测到HSV 特异性抗原 抗原糖蛋白B（gB）存在于 人角质形成细胞（HK），其是HAEM中的损伤部位。 我们现在建议将我们的临床和病理学研究扩展到 分子水平;使用分子病毒学技术， 研究HSV在EM中的作用。 我们建议确定， HSV通过检查受试者的血沉棕黄层在HAEM中传播， 在EM发作之前、期间和之后。 我们还要 确定HSV是否潜伏在HAEM患者的皮肤中， EM皮肤病变和既往受累皮肤的检查 在EM被清除之后。 为了完成这些研究，我们 已经制备了一种包括病毒DNA区域的核糖核酸探针 gB的编码 该探针是HSV特异性的， 对皮克级敏感。 我们将使用机器人探测器 原位杂交技术和斑点杂交， 识别HSV。 我们假设皮肤损伤不仅仅是非- 特异性超敏反应，但HSV特异性 涉及宿主对HK上表达的HSV抗原的应答。 我们 建议使用几种模型来检查损伤机制 细胞毒性。 最后，我们建议研究 使用抗HSV药物，阿昔洛韦， 来抑制EM

Our previous clinical and pathologic investigations of erythema multiforme (EM) have demonstrated that herpes simplex virus is closely linked to EM and that herpes-associated EM (HAEM) is the most commonly observed form of EM. We have further obsrved that recurrent EM is virtually always HSV associated. In the skin obtained from active lesions of EM we have detected a HSV specific antigen. The antigen, glycoprotein B (gB) is found within human keratinocytes (HK), which is the site of injury in HAEM. We now propose to extend our clinical and pathologic studies to the molecular level; using molecular virology techniques to investigate the role of HSV in EM. We propose to determine if HSV disseminates in HAEM by examining buffy coats of subjects, before, during and after episodes of EM. We also wish to determine if HSV is latent in the skin of patients with HAEM by examination of EM skin lesions and of previously involved skin sites after the EM has cleared. To complete these studies we have prepared a riboprobe which includes the region of viral DNA that encodes for gB. The probe is HSV-specific and highly sensitive to the picogram level. We will use the roboprobe for in situ hybridization techniques and dot-blot hybridization to identify HSV. We hypothesize that the cutaneous injury is not merely non- specific hypersensitivity as previously thought, but HSV-specific involving the host response to HSV antigens expressed on HK. We proposed to examine the mechanism of injury using several models of cytotoxicity. Finally, we propose to study the effect of therapeutic intervention in EM using an anti-HSV drug, acyclovir, to suppress EM.