In Vitro Approach To Problems of Clinical Allergy

描述(申请人提供)：35年来，这项资助一直支持 涉及治疗过敏性疾病的研究。在最后的25个案例中， 我们的重点一直是昆虫过敏。1976年，我们展示了当时的标准 全身提取物的治疗免疫疗法与 安慰剂，而用毒液治疗消除了对叮咬的反应。毒液 免疫疗法迅速成为标准疗法。指导方针要求提供所有历史 阳性，皮试阳性的患者接受毒液免疫治疗，但这 涉及整整3%的美国公民。欧洲工人报告说， 大约8年前，足足75%的水疱性过敏患者呈阳性 皮肤测试不会对刺痛有反应。我们已经确认了这项工作。我们的现在 目标建立在我们最近开发的实验室测试的事实上 它预测98%的患者将不会有反应。 我们希望继续开展这项工作，以开发实验室测试，以确定 谁会对斯汀做出反应。我们受到低反应速度的限制，因此也是如此 与宾夕法尼亚州农村的一名同事联手获得更多 病人。我们还将尝试更接近于现场的刺痛 通常发生在病人锻炼的时候。更好的是，我们将努力 看看我们能不能用浓度很高的毒液 与毒液中的血管扩张剂，如组胺和激动素。我们 最近发现，目前的诊断方法，即蛇毒皮肤 测试和RAST是不够的。病史呈阳性皮肤测试呈阳性 阴性患者对刺痛的反应率相同。我们会试着 通过透析和/或使用提纯的材料来改进皮肤测试材料 黄夹克的主要过敏原，VES v5。我们希望将我们的研究扩展到 较大的局部反应，其发生率是全身反应的3-5倍 反应。在大约三分之一的此类患者中，反应充分 需要用类固醇药物治疗是痛苦的。我们打算证明 免疫疗法将消除这种反应。 最后，我们正在与一家名为Dyavax Technologies的公司合作 Corporation*，该公司已表明过敏原与细菌有关 含有CpG mot的寡核苷酸可降低过敏性和 将Th2-更改为类似Th1的响应。因为有50%的全身反应 率环毒免疫治疗，我们希望危害小而效果好 用于免疫治疗的材料。最后，我们最新的研究表明 并不是所有的患者都能在5年后停止蛇毒免疫治疗，这是 目前的建议是，并不是所有的儿童长大后都会对昆虫过敏。 我们需要继续研究这些患者，以开发出最有用的临床 指导方针。

DESCRIPTION (provided by applicant): For 35 years, this grant has supported studies involving the treatment of allergic diseases. For the last 25 of these, our focus has been on insect allergy. In 1976, we showed that the then standard treatment immunotherapy, with whole body extract, was no different than placebo, whereas treatment with venoms eliminated the reaction to sting. Venom immunotherapy rapidly became standard. Guidelines call for all history positive, skin test positive patients to receive venom immunotherapy, but this involves fully 3% of all United States citizens. European workers reported, about 8 years ago, that fully 75% of vespid allergic individuals with positive skin tests would not react to sting. We have confirmed that work. Our present goals build on the fact that we have very recently, developed laboratory tests which predict 98% of those patients who will not react. We would like to continue that work to develop laboratory tests, which identify who will react on sting. We are limited by the low reaction rate and so have joined forces with a colleague in rural Pennsylvania to obtain additional patients. We will also try to more closely approximate the field sting which usually takes place when patients are exercising. Even better, we will try to see if we can mimic a sting using very high concentrations of venom together with the vasodialators which are in venoms, such as histamine and kinins. We have recently found that the current diagnostic methods, that is the venom skin test and RAST, are not adequate. History positive, skin test positive and negative patients have the same rate of reactions to sting. We will tempt to improve the skin test material by dialysis and/or working with the purified major allergen of yellow jackets, Ves v 5. We hope to extend our studies into large local reactions, which occur 3-5 times more commonly than systemic reactions. In about one-third of such patients, the reactions are sufficiently painful to require medication with steroids. We intend to demonstrate that immunotherapy will ablate this type of reaction. Finally, we are collaborating with a company, Dynavax Technologies Corporation*, which has shown that allergens linked to bacterial oligonucleotides containing the CpG mot have decreased allergenicity and changed a Th2- to a Th1-like response. Since there is a 50% systemic reaction rate ring venom immunotherapy, we would like less harmful and more effective materials for immunotherapy. Finally, our most recent studies have shown that not all patients can discontinue venom immunotherapy after 5 years, which is the current recommendation, and that not all children outgrow insect allergy. We need to continue to study these patients to develop the most useful clinical guidelines.