Immune progression and plasticity in relation to child age

与儿童年龄相关的免疫进展和可塑性

• 批准号: 10579324
• 负责人: WAYNE G SHREFFLER
• 金额: $ 23.5万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10579324
• 关键词: Accidents; Age; Allergens; Allergy to peanuts; Child; Chronic; Clinical; Clinical Data; Consumption; Disease remission; Disparity; Dose; Exercise; Goals; Hypersensitivity; IgE; Immune; Immunologics; Immunotherapy; Industry; Ingestion; Intervention; Intervention Studies; Non-Steroidal Anti-Inflammatory Agents; Outcome; Patients; Publishing; Reaction; Sampling; School-Age Population; Testing; Therapeutic; Time; Treatment Efficacy; age related; clinically significant; cofactor; desensitization; oral immunotherapy; phase III trial; treatment risk

Oral immunotherapy (OIT) for peanut allergy has been the most studied interventional strategy for children with established allergy and is now the focus of an industry-sponsored phase 3 trial – one of the first in a field currently lacking any approved therapy. For the majority of patients treated, they can tolerate OIT adequately and it induces a substantial shift in the dose of allergen that elicits a reaction to a level well above most accidental ingestions, so long as they maintain consistent therapeutic exposure. This transient state of clinical protection, or `desensitization' as it is often referred to by allergists, is deemed an acceptable outcome by many patients, but there are limitations. For one, when in a desensitized state, unlike someone who is in true remission, there is some ongoing risk of treatment-associated reactions, especially with co-factors of inter-current illness, exercise, NSAID use, and others. Secondly, many patients find it very difficult to adhere to a chronic therapy. Therefore, even without the goal of ad lib peanut consumption, OIT would be a more beneficial intervention if efficacy were more durable and easier to maintain after an initial course of treatment. In fact, from several studies of children from school age and above, about 1/3 of patients do achieve a more durable benefit from OIT, defined by being able to avoid peanut for a month or more and remaining clinical tolerant to a clinically significant exposure. Those patients who achieve this more robust benefit tend to have lower peanut specific IgE levels at baseline, suggesting that there may be important immunological differences about them, but they are otherwise hard to identify. A just published study, however, suggests that young age at the time of OIT may also be associated with persistent tolerance after immunotherapy. This proposal would directly test the hypothesis that younger patients achieve OIT-induced tolerance at higher rates and would generate the clinical data and samples necessary to explore the immune mechanisms of age-dependent disparities.

对花生过敏的口服免疫疗法（OIT）一直是研究毒素的介入策略最多的 对于已建立过敏的儿童，现在是行业赞助的第三阶段试验的重点 - 目前缺乏任何批准疗法的领域中的第一个。大多数患者 经过处理，它们可以充分耐受OIT，并引起剂量的实质转移 只要它们会引起对大多数意外摄入水平的反应，只要它们 保持一致的热暴露。这种短暂的临床保护状态，或 过敏者经常提到的“脱敏”被认为是可以接受的结果 许多患者，但存在局限性。首先，当处于脱敏状态时，与某人不同 真正缓解的人，有一些与治疗相关反应的风险， 尤其是与流行疾病，运动​​，NSAID使用等的共同因素。第二， 许多患者发现很难遵守慢性疗法。因此，即使没有 AD LIB花生消费的目标，如果生效是有效的，OIT将是更有益的干预 初步治疗后，更耐用，更容易维护。实际上，来自几个 研究年龄及以上儿童的研究，大约有1/3的患者确实达到了更耐用的患者 OIT的益处，通过能够避免花生一个月或更长时间而定义 对临床显着暴露的临床耐受性。那些实现这一更强大的患者 益处在基线时往往具有较低的花生特异性IgE水平，这表明可能存在 它们的重要免疫学差异，但否则它们很难识别。公正 然而，已发表的研究表明，OIT时代的年龄也可能与之相关 免疫疗法后具有持续的耐受性。该建议将直接检验假设 年轻的患者以较高的速率实现OIT诱导的公差，并将产生 探索依赖年龄的免疫机制所需的临床数据和样品 差异。

项目成果

Updating the CoFAR Grading Scale for Systemic Allergic Reactions in Food Allergy.

• DOI: 10.1016/j.jaci.2021.12.789
• 发表时间: 2022-06
• 期刊: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
• 影响因子: 14.2
• 作者: Chinthrajah, R. Sharon;Jones, Stacie M.;Kim, Edwin H.;Sicherer, Scott H.;Shreffler, Wayne;Lanser, Bruce J.;Atri, Negin;Babineau, Denise C.;Adelman, Daniel C.;Iqbal, Ahmar;Limb, Susan L.;Spergel, Amanda K. Rudman;Togias, Alkis;Wood, Robert A.
• 通讯作者: Wood, Robert A.