IN VITRO APPROACH TO PROBLEMS OF CLINICAL ALLERGY

在美国，所有有过敏史的成年患者都会 昆虫叮咬和阳性毒液皮肤乳头用全身治疗 萃取物。我们已经证明，与这一标准治疗相反， 昆虫叮咬过敏，毒液免疫疗法是有效的。最近， 荷兰的调查人员发现，如果它们刺痛历史呈阳性 皮肤测试呈阳性的患者，超过70%没有反应，而且，他们 争辩，不需要治疗。美国不完整的研究发现非反应堆较少 关于挑战刺痛。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有反应 刺痛和不会刺痛。目前的建议是基于 假设欧洲的研究部分是正确的，而且是正确的 没有必要治疗像我们现在这样多的病人。我们将重复他们的 工作，专注于反应较轻的患者，并解决 那项研究：是否一刺就能预测反应的问题 到随后的叮咬。我们还假设临床保护不受 过敏原免疫治疗的结果是一种与免疫无关的机制 对免疫球蛋白封闭抗体的影响。过敏原多肽的免疫治疗导致 再次暴露于变应原时不太直接的过敏反应。我们会 用主要的黄色外套抗原5的多肽免疫患者 毒液过敏原。使用毒液蛋白的标准免疫热疗可导致 经常出现较大的局部反应，较少出现全身过敏反应。 多肽免疫疗法不会引起任何即时反应，但有 通常是一种延迟的、轻微的“类过敏”反应，我们认为 由于产生了一种类似HRF的细胞因子。我们已经开发出一种 确定这一响应的性质的详细协议。最后， 这些研究的主要目标是使用100或更多的蜇 患者开发参数来预测哪些人会有 对叮咬的反应。在目前的工作中，我们计划不仅要研究 免疫球蛋白水平，但炎症细胞活化，细胞因子 产生量、血液和尿液组胺水平以及类胰蛋白酶水平。此外， 根据先前研究的结果，我们还将研究 激动素凝血通路的激活。 毒液免疫疗法(VIT)是基于感知的高风险而推荐的 (&gt；50%)未来系统反应(SR)，对SR恶化的恐惧和缺乏 一种特殊的预后测试。这个陷阱挑战计划试图定义 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 在监控的临床环境中进行刺痛，患者被 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，刺痛挑战是 52例患者，平均年龄45岁，男34岁，女18岁。VST呈阳性 黄夹克(YJ)52例，蜜蜂(HB)12例。这个 临床病史分为轻度(14例)、中度(20例)、中度- 严重(14)或可疑(4)；以前的SR模式包括单一 (29)或多个(23)反应，顺序或多个刺痛(19)。这个 自上次SR以来的中位数时间为2年(范围0-24)；超过10年 10例(5例为儿童期)。诱人挑战引发的系统性挑战 症状9例(17%)，中-重度3例，中度2例，轻度4例。 另有7人出现临界性反应。没有比这更糟糕的反应 病人以前的SR。反应的频率和严重程度更高 在既往有中重度SR的患者中(36%)比在 轻-中度既往SR(10%)。低反应速度很可能是 与我们的许多患者具有低风险(轻度SR、远程SR、 多个/顺序刺)。尽管如此，这些患者中的每个人几乎都会 当然，过敏症专科医生建议他们接受维生素T治疗。 我们的结论是，有一些临床参数可能会区分 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 多种临床和免疫学因素在脑出血中的作用 对昆虫叮咬的反应。

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.