1型和3型干扰素产生的发育调控以及婴儿感染与哮喘发展的风险(JACI)
2018/11/13
摘要
背景：婴儿时期与病毒相关的下呼吸道感染(fLRI)已被确定为持续性喘息发展的危险因素。我们假设在这段时间内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，可能是潜在风险的决定因素。
目的：探讨出生后先天干扰素反应能力的发育与早期感染易感性及持续性喘息的关系。
方法：受试者来自出生队列中哮喘/过敏高危人群的一个子集，并测定了脐带血细胞(n=151)对病毒模拟增殖的反应产生17 T1/3干扰素的能力。我们调查了新生儿干扰素反应与婴儿期下呼吸道感染史、喘息史至5年、4年(n=160)和10年(n=125)后继发先天免疫能力完善之间的关系。
结果：在出生时测试的17个先天性干扰素中，受试者平均产生2.6±0.3个，其中24%没有产生T1/3干扰素。这些出生时未产生T1/3干扰素的婴儿，5岁时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)的风险相对于那些产生T1/3IFNs的风险增高，而婴儿喘息LRI或短暂早期喘息的风险不受影响。此外，经历过fLRI的婴儿随后在1年到4年之间表现出T1/3IFN反应能力的加速发展。
结论：T1/3干扰素的反应能力在出生时表现出强烈的发育受限。这种效应最强的婴儿在婴儿期和随后的持续喘息期间出现严重呼吸道感染的风险明显增加。
Developmental regulation of type 1 and type 3 IFN production and risk for infant infections and asthma development
Patrick G H, et al. J Allergy Clinlmmunol 2018 sep 11
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.
Objective：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：婴儿时期与病毒相关的下呼吸道感染(fLRI)已被确定为持续性喘息发展的危险因素。我们假设在这段时间内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，可能是潜在风险的决定因素。
目的：探讨出生后先天干扰素反应能力的发育与早期感染易感性及持续性喘息的关系。
方法：受试者来自出生队列中哮喘/过敏高危人群的一个子集，并测定了脐带血细胞(n=151)对病毒模拟增殖的反应产生17 T1/3干扰素的能力。我们调查了新生儿干扰素反应与婴儿期下呼吸道感染史、喘息史至5年、4年(n=160)和10年(n=125)后继发先天免疫能力完善之间的关系。
结果：在出生时测试的17个先天性干扰素中，受试者平均产生2.6±0.3个，其中24%没有产生T1/3干扰素。这些出生时未产生T1/3干扰素的婴儿，5岁时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)的风险相对于那些产生T1/3IFNs的风险增高，而婴儿喘息LRI或短暂早期喘息的风险不受影响。此外，经历过fLRI的婴儿随后在1年到4年之间表现出T1/3IFN反应能力的加速发展。
结论：T1/3干扰素的反应能力在出生时表现出强烈的发育受限。这种效应最强的婴儿在婴儿期和随后的持续喘息期间出现严重呼吸道感染的风险明显增加。
（复旦大学附属中山医院呼吸科 魏婷婷 摘译 李文 扬审校）
（J Allergy Clinlmmunol 2018 sep 11）
（J Allergy Clinlmmunol 2018 sep 11）
Developmental regulation of type 1 and type 3 IFN production and risk for infant infections and asthma development
Patrick G H, et al. J Allergy Clinlmmunol 2018 sep 11
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.
Objective：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.
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