Telethon Kids Institute, University of Western Australia, Perth, Australia.
Telethon Kids Institute, University of Western Australia, Perth, Australia.
J Allergy Clin Immunol. 2019 Mar;143(3):1176-1182.e5. doi: 10.1016/j.jaci.2018.08.035. Epub 2018 Sep 12.
Virus-associated febrile lower respiratory tract infections (fLRIs) during infancy have been identified as risk factors for persistent wheeze development. We hypothesized that variations in innate immune defense capacity during this period, as exemplified by production of type 1 and 3 interferons (T1/3IFNs), might be an underlying determinant of risk.
We sought to investigate relationships between postnatal development of innate interferon response capacity and susceptibility to early infections and persistent wheeze.
We studied a subset of subjects from a birth cohort at high risk for asthma/allergy and determined the capacity of cord blood cells (n = 151) to produce any of a panel of 17 T1/3IFNs in response to the viral mimic polyinosinic-polycytidylic acid using a sensitive PCR assay. We investigated relationships between neonatal interferon responses and lower respiratory tract infection history during infancy, wheezing history to 5 age years, and ensuing maturation of innate immune capacity by age 4 years (n = 160) and 10 years (n = 125).
Although cohort subjects produced an average of 2.6 ± 0.3 of the 17 innate interferons tested at birth, 24% showed no T1/3IFN production. This nonproducer subgroup showed increased risk for infant fLRIs (odds ratio, 2.62; 95% CI, 1.14-6.06; P = .024) and persistent wheeze (odds ratio, 4.24; 95% CI, 1.60-11.24; P = .004) at age 5 years relative to those producing 1 or more T1/3IFNs, whereas risk for infant wheezy lower respiratory tract infections or "transient early wheeze" was unaffected. Moreover, infants who experienced fLRIs subsequently demonstrated accelerated development of T1/3IFN response capacity between 1 and 4 years of age.
T1/3IFN response capacity appears strongly developmentally constrained at birth. Infants in whom this negative regulation is strongest manifest increased risk for severe respiratory tract infections during infancy and subsequent persistent wheeze.
婴儿期与病毒相关的发热性下呼吸道感染（fLRIs）已被确定为持续性喘息发展的危险因素。我们假设，在此期间固有免疫防御能力的变化，例如 1 型和 3 型干扰素（T1/3IFNs）的产生，可能是风险的潜在决定因素。
我们旨在研究出生后固有干扰素反应能力的发展与早期感染和持续性喘息易感性之间的关系。
我们研究了高哮喘/过敏风险的出生队列中的一部分受试者，并使用敏感的 PCR 测定法，确定了脐带血细胞（n=151）对病毒模拟物多聚肌苷酸-多聚胞苷酸产生任何 17 种 T1/3IFN 的能力。我们调查了新生儿干扰素反应与婴儿期下呼吸道感染史、5 岁时喘息史以及 4 岁（n=160）和 10 岁（n=125）时固有免疫能力的成熟之间的关系。
尽管队列受试者在出生时平均产生了 17 种测试的固有干扰素中的 2.6±0.3，但有 24%的人没有产生 T1/3IFN。与产生 1 种或多种 T1/3IFN 的受试者相比，非生产者亚组婴儿 fLRIs（优势比，2.62；95%CI，1.14-6.06；P=0.024）和持续性喘息（优势比，4.24；95%CI，1.60-11.24；P=0.004）的风险增加，而婴儿喘息性下呼吸道感染或“短暂性早期喘息”的风险不受影响。此外，经历 fLRIs 的婴儿在 1 至 4 岁之间表现出固有 T1/3IFN 反应能力的加速发展。
T1/3IFN 反应能力在出生时似乎受到强烈的发育限制。在此负调控最强的婴儿中，婴儿期严重呼吸道感染和随后持续性喘息的风险增加。
