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: 10416402
• 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/10416402
• 关键词: Immune; progression; plasticity; relation; child

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.

花生过敏的口服免疫疗法（OIT）是研究最多的干预策略 针对已确定过敏的儿童，现在是行业赞助的第 3 阶段试验的重点 – 目前尚缺乏任何经批准的治疗方法的领域中的第一个。对于大多数患者来说 经过治疗后，他们可以充分耐受 OIT，并且会引起剂量的实质性变化 引起反应水平远高于大多数意外摄入的过敏原，只要它们 保持一致的治疗暴露。这种暂时的临床保护状态，或 过敏症专家经常提到的“脱敏”被认为是可接受的结果 患者很多，但也有局限性。其一，当处于脱敏状态时，与其他人不同 谁处于真正的缓解期，存在一些与治疗相关的反应的持续风险， 尤其是并发疾病、运动、非甾体抗炎药使用等辅助因素。第二， 许多患者发现很难坚持长期治疗。因此，即使没有 随意食用花生的目标，如果功效有效，OIT 将是一种更有益的干预措施 在初始疗程后更耐用且更容易维持。事实上，从几 对学龄及以上儿童的研究表明，大约 1/3 的患者确实实现了更持久的 从 OIT 中受益，定义为能够一个月或更长时间不吃花生，并且剩余时间 临床耐受具有临床意义的暴露。那些实现这一目标的患者更加坚强 基线时花生特异性 IgE 水平往往较低，这表明可能存在 它们之间有重要的免疫学差异，但很难通过其他方式识别。一个公正的 然而，已发表的研究表明，OIT 时的年轻年龄也可能与 免疫治疗后具有持续耐受性。该提案将直接检验假设 年轻患者以更高的速率实现 OIT 诱导的耐受性，并且会产生 探索年龄依赖性免疫机制所需的临床数据和样本 差异。