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: 9308334
• 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 2022-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9308334
• 关键词: 5 year old; Adult; Age; Allergens; Allergic; Allergic Disease; Allergy to peanuts; Biological; Child; Childhood; Chronic; Clinical; Clinical Data; Clinical Research; Clinical Trials; Cohort Analysis; Consumption; Data; Databases; Diagnosis; Disease remission; Dose; Employee Strikes; Exercise; Food; Food Hypersensitivity; Fostering; General Hospitals; Goals; Health; Human; Hypersensitivity; IgE; Immune; Immune system; Immunologics; Immunology; Immunotherapy; Individual; Industry; Ingestion; Intervention; Intervention Studies; Intervention Trial; Leadership; Life; Massachusetts; National Institute of Allergy and Infectious Disease; Natural History; Oral; Outcome; Participant; Patients; Phase; Phase III Clinical Trials; Phenotype; Population; Population Study; Prevention; Production; Publishing; Randomized Controlled Trials; Reaction; Recruitment Activity; Reporting; Research; Research Infrastructure; Research Personnel; Resolution; Risk; Sampling; School-Age Population; Site; Spontaneous Remission; Testing; Therapeutic; Time; Toddler; Treatment Efficacy; Work; age related; career; clinical remission; clinically significant; cohort; desensitization; food antigen; high risk infant; industry partner; innovation; interest; operation; oral immunotherapy; primary outcome; response; skills

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 目前是一项由行业赞助的3期临床试验的重点 - 这是目前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 治疗后，他们可以充分耐受OIT，并诱导OIT剂量的实质性变化。 过敏原，激发反应的水平远远高于大多数意外摄入，只要他们 保持一致的治疗暴露。这种临床保护的暂时状态，或 过敏症专家经常提到的“脱敏”被认为是一种可接受的结果， 患者很多，但也有局限性。首先，当处于一种麻木状态时， 对于真正缓解的患者，仍存在一些治疗相关反应的持续风险， 特别是伴随并发疾病、运动、NSAID使用等因素。第二、 许多患者发现很难坚持长期治疗。因此，即使没有 目标的随意花生消费，OIT将是一个更有益的干预，如果疗效 在初始疗程后更持久且更容易维持。事实上，从几个 从学龄及以上儿童的研究中，约有1/3的患者做到了较持久 从OIT中受益，定义为能够避免花生一个月或更长时间， 临床耐受临床显著暴露。达到这一点的患者 在基线时，花生特异性IgE水平较低，这表明可能存在 重要的免疫学差异，但它们很难识别。公正 然而，一项已发表的研究表明，OIT时的年轻年龄也可能与 免疫治疗后持续耐受。这一提议将直接检验 年轻患者以更高的速率获得OIT诱导的耐受性， 临床数据和必要的样本，以探索免疫机制的年龄依赖性 差距。