Smit Eva R, Romijn Michelle, Langerhorst Pieter, van der Zwaan Carmen, van der Staaij Hilde, Rotteveel Joost, van Kaam Anton H, Fustolo-Gunnink Suzanne F, Hoogendijk Arie J, Onland Wes, Finken Martijn J J, van den Biggelaar Maartje
Department of Molecular Hematology, Sanquin Research, Amsterdam, the Netherlands.
Department of Neonatology, Amsterdam UMC location University of Amsterdam, Amsterdam, the Netherlands.
Pediatr Res. 2024 Aug 16. doi: 10.1038/s41390-024-03481-0.
Preterm infants, especially those born small for gestational age (SGA), are at risk of short-term and long-term health complications. Characterization of changes in circulating proteins postnatally in preterm infants may provide valuable fundamental insights into this population. Here, we investigated postnatal developmental patterns in preterm infants and explored protein signatures that deviate between SGA infants and appropriate for gestational age (AGA) infants using a mass spectrometry (MS)-based proteomics workflow.
Longitudinal serum samples obtained at postnatal days 0, 3, 7, 14, and 28 from 67 preterm infants were analyzed using unbiased MS-based proteomics.
314 out of 833 quantified serum proteins change postnatally, including previously described age-related changes in immunoglobulins, hemoglobin subunits, and new developmental patterns, e.g. apolipoproteins (APOA4) and terminal complement cascade (C9) proteins. Limited differences between SGA and AGA infants were found at birth while longitudinal monitoring revealed 69 deviating proteins, including insulin-sensitizing hormone adiponectin, platelet proteins, and 24 proteins with an annotated function in the immune response.
This study shows the potential of MS-based serum profiling in defining circulating protein trajectories in the preterm infant population and its ability to identify longitudinal alterations in protein levels associated with SGA.
Postnatal changes of circulating proteins in preterm infants have not fully been elucidated but may contribute to development of health complications. Mass spectrometry-based analysis is an attractive approach to study circulating proteins in preterm infants with limited material. Longitudinal plasma profiling reveals postnatal developmental-related patterns in preterm infants (314/833 proteins) including previously described changes, but also previously unreported proteins. Longitudinal monitoring revealed an immune response signature between SGA and AGA infants. This study highlights the importance of taking postnatal changes into account for translational studies in preterm infants.
早产儿，尤其是那些出生时小于胎龄（SGA）的婴儿，面临短期和长期健康并发症的风险。对早产儿出生后循环蛋白变化的特征分析可能为这一人群提供有价值的基础见解。在此，我们研究了早产儿出生后的发育模式，并使用基于质谱（MS）的蛋白质组学工作流程探索了SGA婴儿和适于胎龄（AGA）婴儿之间存在差异的蛋白质特征。
使用基于MS的非靶向蛋白质组学分析了67例早产儿在出生后第0、3、7、14和28天采集的纵向血清样本。
833种定量血清蛋白中有314种在出生后发生变化，包括先前描述的免疫球蛋白、血红蛋白亚基与年龄相关的变化，以及新的发育模式，如载脂蛋白（APOA4）和末端补体级联（C9）蛋白。出生时SGA婴儿和AGA婴儿之间的差异有限，而纵向监测发现了69种差异蛋白，包括胰岛素增敏激素脂联素、血小板蛋白，以及24种在免疫反应中具有注释功能的蛋白。
本研究显示了基于MS的血清分析在确定早产儿群体中循环蛋白轨迹方面的潜力，以及识别与SGA相关的蛋白质水平纵向变化的能力。
早产儿循环蛋白的出生后变化尚未完全阐明，但可能导致健康并发症的发生。基于质谱的分析是一种研究材料有限的早产儿循环蛋白的有吸引力的方法。纵向血浆分析揭示了早产儿出生后与发育相关的模式（314/833种蛋白质），包括先前描述的变化，但也有先前未报道的蛋白质。纵向监测揭示了SGA婴儿和AGA婴儿之间的免疫反应特征。本研究强调了在早产儿的转化研究中考虑出生后变化的重要性。
