The Truncated Splice Variant of the Granulocyte-Macrophage-Colony-Stimulating Factor Receptor β- Chain in Peripheral Blood Serves as Severity Biomarker of Respiratory Failure in Newborns
The Truncated Splice Variant of the Granulocyte-Macrophage-Colony-Stimulating Factor Receptor β- Chain in Peripheral Blood Serves as Severity Biomarker of Respiratory Failure in Newborns
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DOI：
10.1159/000513356
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发表时间：
2021-03-30
期刊：
影响因子：
2.5
通讯作者：
Rieger-Fackeldey, Esther
中科院分区：
文献类型：
--
作者：
Schulte, Verena;Sipol, Alexandra;Rieger-Fackeldey, Esther
背景：粒细胞-巨噬细胞集落刺激因子(GM-CSF)在肺表面活性物质动态平衡中起重要作用。β(C)是GM-CSF受体(GM-CSF-R)的一个亚单位，它的激活介导肺内表面活性物质的分解代谢。β(IT)是β(C)的一种生理性截短亚型，被认为是β(C)的生理性抑制物。目的：探讨新生儿外周血中β(IT)和β(C)的比值及其与新生儿呼吸衰竭程度的关系。方法：我们对出生时有不同程度呼吸损伤的新生儿进行了前瞻性队列研究。呼吸状态通过从无呼吸损害(0)到有创呼吸支持(3)的评分进行评估。用实时定量聚合酶链式反应检测外周血细胞中β(IT)和β(C)的表达。β(IT)表达定义为β(IT)与β(C)的比值，与呼吸评分相关。结果：59例新生儿中均有β(IT)表达，呼吸系统疾病(评分2，3)新生儿的β(IT)水平高于呼吸健康新生儿(评分0.066，1；P=0.05)。重症新生儿(评分3)的β(IT)显著高于健康新生儿([评分0]，p=0.010)。健康早产儿的β(IT)表达显著高于健康足月儿(p=0.019)。结论：β(IT)在新生儿中有表达，呼吸系统疾病新生儿的表达高于呼吸系统健康新生儿。我们推测，β(IT)在出生后肺适应中可能具有保护作用，作为β(C)的生理抑制物，从而维持呼吸系统疾病新生儿的表面活性物质。
Background: The granulocyte-macrophage-colony-stimulating factor (GM-CSF) plays an important role in surfactant homeostasis. beta(C) is a subunit of the GM-CSF receptor (GM-CSF-R), and its activation mediates surfactant catabolism in the lung. beta(IT) is a physiological, truncated isoform of beta(C) and is known to act as physiological inhibitor of beta(C). Objective: The aim of this study was to determine the ratio of beta(IT) and beta(C) in the peripheral blood of newborns and its association with the degree of respiratory failure at birth. Methods: We conducted a prospective cohort study in newborns with various degrees of respiratory impairment at birth. Respiratory status was assessed by a score ranging from no respiratory impairment (0) to invasive respiratory support (3). beta(IT) and beta(C) expression were determined in peripheral blood cells by real-time PCR. beta(IT) expression, defined as the ratio of beta(IT) and beta(C), was correlated with the respiratory score. Results: beta(IT) expression was found in all 59 recruited newborns with a trend toward higher beta(IT) in respiratory ill (score 2, 3) newborns than respiratory healthy newborns ([score 0, 1]; p = 0.066). Seriously ill newborns (score 3) had significantly higher beta(IT) than healthy newborns ([score 0], p = 0.010). Healthy preterm infants had significantly higher beta(IT) expression than healthy term infants (p = 0.019). Conclusions: beta(IT) is expressed in newborns with higher expression in respiratory ill than respiratory healthy newborns. We hypothesize that beta(IT) may have a protective effect in postnatal pulmonary adaptation acting as a physiological inhibitor of beta(C) and, therefore, maintaining surfactant in respiratory ill newborns.