IN VITRO APPROACH TO PROBLEMS OF CLINICAL ALLERGY

在美国，所有有过敏史的成年患者， 昆虫叮咬和阳性毒液皮肤乳头用全身治疗 萃取物我们已经表明，与这种标准治疗相反， 昆虫叮咬过敏，毒液免疫疗法有效。最近， 荷兰的调查人员发现， 皮试阳性的病人，百分之七十以上没有反应， 争论，不需要治疗。不完整的美国研究发现， 挑战斯汀美国和荷兰的调查人员都没有 能够开发诊断参数来预测哪些患者会做出反应， 哪些不会目前的建议是根据 假设欧洲的研究部分是正确的， 不需要像现在这样治疗这么多病人。我们将重复他们的 工作，专注于反应较轻的患者，并解决 这项研究的问题是， 后来的刺。我们还假设， 过敏原免疫治疗是由免疫无关的机制引起的， IgG阻断抗体。过敏原肽免疫治疗导致 在再次暴露于过敏原时的较低的立即过敏反应。我们将 用来自抗原5的肽免疫病人， 毒液过敏原标准的免疫疗法与毒液蛋白导致 频繁出现大的局部反应，较少发生全身过敏反应。 肽免疫疗法不会引起任何立即反应，但有 通常是一种延迟的和轻微的“过敏样”反应，我们认为这是 这是由于HRF样细胞因子的产生。我们已经开发出一种 详细的协议，以确定这种反应的性质。最后 这些研究的主要目标是使用一百或更多的毒刺 患者开发参数，预测哪些人将有 被蜇后的反应在目前的工作中，我们计划不仅研究 免疫球蛋白水平，但炎症细胞活化，细胞因子 生产，血液和尿液组胺水平和类胰蛋白酶水平。此外，本发明还 根据先前的研究结果，我们还将研究 激活激肽凝血途径。 毒液免疫疗法（VIT）是基于感知的高风险建议 （>50%）的未来全身反应（SR），担心SR恶化和缺乏 一种特殊的预后测试这个毒刺挑战计划旨在定义 与SR风险较低相关的临床和实验室特征 在有SR病史和毒液皮肤试验（VST）阳性的患者中。昆虫 在监测的临床环境中进行刺痛， 观察SR的客观体征和主观症状。 在350名报告“严重”刺痛反应的患者中， 对52名患者进行了研究：平均年龄45岁，34名男性，18名女性。VST呈阳性， 黄夹克（YJ）52例，蜜蜂（HB）12例。的 临床病史分为轻度（14例）、中度（20例）、中度- 重度（14）或可疑（4）;既往SR模式包括单次 (29)或多个（23）反应、连续或多个刺痛（19）。的 自上次SR以来的中位时间为2年（范围0-24）;超过10年 10例患者（5例为儿童）。刺痛激发引起全身性 9例患者（17%）有症状; 3例中度-重度，2例中度，4例轻度。 另外7人有临界反应。没有什么反应比 患者既往SR。反应的频率和严重程度较高 中重度既往SR患者（36%）比 轻度-中度既往SR（10%）。低反应率很可能是 与我们的许多低风险患者（轻度SR，远程SR， 多个/顺序的刺痛）。尽管如此，这些病人中的每一个几乎都会 当然，过敏症专科医生建议接受维生素T。 我们的结论是，有临床参数，可以区分 SR风险低的患者可以安全地放弃VIT。更多 需要对患者进行有监督的挑战研究，以准确定义 许多临床和免疫学因素参与了 SR到昆虫叮咬。

In the United States, all adult patients with a history of anaphylaxis on insect sting and a positive venom skin teat are treated with whole body extracts. We have shown that, contrary to this standard treatment for insect sting allergy, venom immunotherapy is effective. Recently, investigators in Holland have found that if they sting history-positive skin test-positive patients, more than 70% have no reaction, and, they contend, need no therapy. Incomplete US studies found fewer non-reactors on challenge sting. Neither the US nor the Dutch investigators have been able to develop diagnostic parameters to predict which patients will react to stings and which will not. The current proposal is based on the hypothesis that the European studies are, in part, correct and that it is unnecessary to treat as many patients as we do now. We will repeat their work, focusing on patients with milder reactions, and address a flaw in that study: the question of whether a single sting predicts the reaction to subsequent stings. We also hypothesize that clinical protection from allergen immunotherapy results from a mechanism of immunization unrelated to IgG blocking antibodies. Immunotherapy with allergen peptides leads to a lesser immediate allergic response on re-exposure to allergen. We will immunize patients with peptides from antigen 5, the major yellow jacket venom allergen. Standard immunotherpay with venom proteins leads to frequent large local reactions and, less often, to systemic anaphylaxis. Peptide immunotherapy does not cause any immediate reactions, but there is often a delayed and mild "anaphylactic-like" response which we believe is due to the generation of an HRF-like cytokine. We have developed a detailed protocol to ascertain the nature of this response. Finally, the major goal of these studies is to use the stings of a hundred or more patients to develop parameters which predict which individuals will have a reaction to a sting. In the current work, we plan to study not only immunoglobulin levels but inflammatory cell activation, cytokine production, blood and urine histamine levels and tryptase levels. Further, based on the results of earlier studies, we will also study the state of activation of the kinin coagulation pathways. Venom immunotherapy (VIT) is recommended based on perceived high risk (>50%) of future systemic reaction (SR), fear of worsening SR and lack of a specific prognostic test. This sting challenge program seeks to define clinical and laboratory characteristics associated with lower risk of SR in patients with SR history and positive venom skin tests (VST). Insect stings were performed in a monitored clinical setting and patients were observed for objective signs and subjective symptoms of SR. Of 350 patients who reported "severe" sting reactions, sting challenge was performed on 52 patients: mean age 45 yrs, 34M, 18F. VST was positive to yellow jacket (YJ) in 52 patients and honeybee (HB) in 12 patients. The clinical history was classified as mild (14), moderate (20), moderate- severe (14) or questionable (4); patterns of previous SR included single (29) or multiple (23) reactions, sequential or multiple stings (19). The median time since the last SR was 2 years (range 0-24); it was over 10 years in 10 patients (5 in childhood). Sting challenge caused systemic symptoms in 9 patients (17%); 3 moderate-severe, 2 moderate, 4 mild. Another 7 had borderline reactions. No reaction was worse than the patient's previous SR. The frequency and severity of reaction was greater in patients with moderate-severe previous SR (36%) than in patients with mild-moderate previous SR (10%). The low reaction rate is most likely related to many of our patients having low risk (mild SR, remote SR, multiple/sequential stings). Still, each of these patients would almost certainly have been advised to receive VIT by an allergist. We conclude that there are clinical parameters that may distinguish patients with low risk of SR who could safely forego VIT. Many more patients need to be studied with supervised challenge to define accurately the contribution of the many clinical and immunologic factors involved in SR to insect stings.