1型和3型IFN产生的发育调节和婴儿感染及哮喘发展的风险
2018/10/24
摘要
背景：婴儿期间病毒相关的发热性下呼吸道感染（fLRI）已被确定为持续性喘息发展的危险因素。我们假设在此期间先天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。本文旨在调查先天干扰素反应能力的产后发展与早期感染和持续性喘息的易感性之间的关系。
方法：我们研究了哮喘/过敏高风险出生队列的一部分受试者，并通过高敏PCR测定确定了脐带血细胞（n=151）产生17种响应病毒模拟聚（I:C）的T1/3IFN的任何一组的能力。我们研究了新生儿干扰素反应与婴儿期下呼吸道感染史，5年喘息史以及随后4年（n=160）和10年（n=125）的先天免疫能力成熟之间的关系。
结果：虽然群组受试者在出生时测试的17种先天性IFN中平均产生2.6±0.3，但24％显示没有T1/3IFN产生。这个非产生者亚组显示5岁时婴儿fLRI（OR2.62[1.14-6.06] p=0.024）和持续性喘息（OR4.24 [1.60-11.24] p=0.004）比≥1T1/ 3IFNs的亚组风险增加，而婴儿喘息性下呼吸道感染或“短暂性早期喘息”的风险未受影响。此外，经历过fLRI的婴儿随后表现出在1年和4年之间T1/3IFN反应能力的加速发展。
结论：T1/3IFN反应能力在出生时似乎受到强烈的发育限制。这种负调节的婴儿表现出婴儿期间严重呼吸道感染和随后持续性喘息的风险增加是最强的。
Developmental regulation of type 1 and type 3 IFN production and risk for infant infections and asthma development.
Holt PG, Mok D, Panda D, Renn L, Fabozzi G, deKlerk NH, Kusel MM, Serralha M, Hollams EM, Holt BJ, Sly PD, Rabin RL.
Abstract
BACKGROUND:Virus-associated febrile lower respiratory tract infections (fLRI) during infancy have been identified as risk factors for persistent wheeze development. We hypothesized that variations in innate immune defence capacity during this period, exemplified by production of types 1 and 3 interferons (T1/3IFNs), may be an underlying determinant of risk. To investigate relationships between postnatal development of innate interferon response capacity and susceptibility to early infections and persistent wheeze.
METHODS:We studied a subset of subjects from a birth cohort at high risk for asthma/allergy, and determined capacity of cord blood cells (n=151) to produce any of a panel of 17 T1/3IFNs in response to the viral mimic poly(I:C), employing a sensitive PCR assay. We investigated relationships between neonatal interferon responses and lower respiratory infection history during infancy, wheezing history to 5Yrs, and ensuing maturation of innate immune capacity by 4Yrs (n=160) and 10Yrs (n=125).
RESULTS:While cohort subjects produced on average 2.6±0.3 of the 17 innate IFNs tested at birth, 24% showed no T1/3IFN production. This non-producer subgroup showed increased risk for infant fLRI (OR 2.62[1.14-6.06]p=0.024) and persistent wheeze (OR 4.24[1.60-11.24]p=0.004) at age 5Yrs relative to those producing ≥1 T1/3IFNs, whereas risk for infant wheezy LRI or "transient early wheeze" was unaffected. Moreover, infants who experienced fLRI subsequently demonstrated accelerated development of T1/3IFN response capacity between 1Yr and 4Yrs.
CONCLUSIONS:T1/3IFN response capacity appears strongly developmentally constrained at birth. Infants in whom this negative regulation is strongest manifest increased risk for severe respiratory infections during infancy and subsequent persistent wheeze.
背景：婴儿期间病毒相关的发热性下呼吸道感染（fLRI）已被确定为持续性喘息发展的危险因素。我们假设在此期间先天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。本文旨在调查先天干扰素反应能力的产后发展与早期感染和持续性喘息的易感性之间的关系。
方法：我们研究了哮喘/过敏高风险出生队列的一部分受试者，并通过高敏PCR测定确定了脐带血细胞（n=151）产生17种响应病毒模拟聚（I:C）的T1/3IFN的任何一组的能力。我们研究了新生儿干扰素反应与婴儿期下呼吸道感染史，5年喘息史以及随后4年（n=160）和10年（n=125）的先天免疫能力成熟之间的关系。
结果：虽然群组受试者在出生时测试的17种先天性IFN中平均产生2.6±0.3，但24％显示没有T1/3IFN产生。这个非产生者亚组显示5岁时婴儿fLRI（OR2.62[1.14-6.06] p=0.024）和持续性喘息（OR4.24 [1.60-11.24] p=0.004）比≥1T1/ 3IFNs的亚组风险增加，而婴儿喘息性下呼吸道感染或“短暂性早期喘息”的风险未受影响。此外，经历过fLRI的婴儿随后表现出在1年和4年之间T1/3IFN反应能力的加速发展。
结论：T1/3IFN反应能力在出生时似乎受到强烈的发育限制。这种负调节的婴儿表现出婴儿期间严重呼吸道感染和随后持续性喘息的风险增加是最强的。
(中日友好医院呼吸与危重症医学科 王瑞茵 摘译 林江涛 审校)
(J Allergy Clin Immunol. 2018 Sep 11. pii: S0091-6749(18)31284-3. doi: 10.1016/j.jaci.2018.08.035. [Epub ahead of print].)
(J Allergy Clin Immunol. 2018 Sep 11. pii: S0091-6749(18)31284-3. doi: 10.1016/j.jaci.2018.08.035. [Epub ahead of print].)
Developmental regulation of type 1 and type 3 IFN production and risk for infant infections and asthma development.
Holt PG, Mok D, Panda D, Renn L, Fabozzi G, deKlerk NH, Kusel MM, Serralha M, Hollams EM, Holt BJ, Sly PD, Rabin RL.
Abstract
BACKGROUND:Virus-associated febrile lower respiratory tract infections (fLRI) during infancy have been identified as risk factors for persistent wheeze development. We hypothesized that variations in innate immune defence capacity during this period, exemplified by production of types 1 and 3 interferons (T1/3IFNs), may be an underlying determinant of risk. To investigate relationships between postnatal development of innate interferon response capacity and susceptibility to early infections and persistent wheeze.
METHODS:We studied a subset of subjects from a birth cohort at high risk for asthma/allergy, and determined capacity of cord blood cells (n=151) to produce any of a panel of 17 T1/3IFNs in response to the viral mimic poly(I:C), employing a sensitive PCR assay. We investigated relationships between neonatal interferon responses and lower respiratory infection history during infancy, wheezing history to 5Yrs, and ensuing maturation of innate immune capacity by 4Yrs (n=160) and 10Yrs (n=125).
RESULTS:While cohort subjects produced on average 2.6±0.3 of the 17 innate IFNs tested at birth, 24% showed no T1/3IFN production. This non-producer subgroup showed increased risk for infant fLRI (OR 2.62[1.14-6.06]p=0.024) and persistent wheeze (OR 4.24[1.60-11.24]p=0.004) at age 5Yrs relative to those producing ≥1 T1/3IFNs, whereas risk for infant wheezy LRI or "transient early wheeze" was unaffected. Moreover, infants who experienced fLRI subsequently demonstrated accelerated development of T1/3IFN response capacity between 1Yr and 4Yrs.
CONCLUSIONS:T1/3IFN response capacity appears strongly developmentally constrained at birth. Infants in whom this negative regulation is strongest manifest increased risk for severe respiratory infections during infancy and subsequent persistent wheeze.
