Plasma proteome changes in cord blood samples from preterm infants

Suski, Maciej; Bokiniec, Renata; Szwarc-Duma, Monika; Madej, Józef; Bujak-Giżycka, Beata; Borszewska−Kornacka, Maria Katarzyna; Książek, Teofila; Grabowska, Agnieszka; Revhaug, Cecilie; Baumbusch, Lars Oliver; Saugstad, Ola Didrik; Pietrzyk, Jacek J; Kwinta, Przemko

doi:10.1038/s41372-018-0150-7

Cited by 12 publications

(19 citation statements)

References 71 publications

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“…The plasma proteome for adults and infants [24] has been previously described, but, to our knowledge, we provide the first comparison of infant plasma and lung fluid protein profile and evidence for the close proportional abundance in the two tissue compartments. This finding indicates that most plasma proteins, irrespective of their size, pass the endothelial/epithelial barrier and accumulate in lung fluid in the injured infant lung similar to the observation in adults with acute respiratory distress syndrome [25].…”

Section: Plos Onementioning

confidence: 81%

Composition and origin of lung fluid proteome in premature infants and relationship to respiratory outcome

et al. 2020

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Background Infants born at extremely low gestational age are at high risk for bronchopulmonary dysplasia and continuing lung disease. There are no early clinical biomarkers for pulmonary outcome and limited therapeutic interventions. Objectives We performed global proteomics of premature infant tracheal aspirate (TA) and plasma to determine the composition and source of lung fluid proteins and to identify potential biomarkers of respiratory outcome. Methods TA samples were collected from intubated infants in the TOLSURF cohort before and after nitric oxide treatment, and plasma was collected from NO CLD infants. Protein abundance was assayed by HPLC/tandem mass spectrometry and Protein Prospector software. mRNA abundance in mid-gestation fetal lung was assessed by RNA sequencing. Pulmonary morbidity was defined as a need for ventilatory support at term and during the first year. Results Abundant TA proteins included albumin, hemoglobin, and actin-related proteins. 96 of 137 detected plasma proteins were present in TA (r = 0.69, p<0.00001). Based on lung RNAseq data, ~88% of detected TA proteins in injured infant lung are derived at least in part from lung epithelium with overrepresentation in categories of cell membrane/secretion and stress/inflammation. Comparing 37 infants at study enrollment (7–14 days) who did or did not develop persistent pulmonary morbidity, candidate biomarkers of both lung (eg., annexin A5) and plasma (eg., vitamin D-binding protein) origin were identified. Notably, levels of free hemoglobin were 2.9-fold (p = 0.03) higher in infants with pulmonary morbidity. In time course studies, hemoglobin decreased markedly in most infants after enrollment coincident with initiation of inhaled nitric oxide treatment. Conclusions We conclude that both lung epithelium and plasma contribute to the lung fluid proteome in premature infants with lung injury. Early postnatal elevation of free hemoglobin and heme, which are both pro-oxidants, may contribute to persistent lung disease by depleting nitric oxide and increasing oxidative/nitrative stress.

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Section: Plos Onementioning

confidence: 81%

Composition and origin of lung fluid proteome in premature infants and relationship to respiratory outcome

et al. 2020

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“…Suski et al completed several studies [ 13 , 14 ] investigating plasma proteome changes in preterm infants comparing gestational ages [ 13 ] and malfunctioning proteins in various signalling pathways [ 14 ]. Utilising a tandem MS approach they were able to identify proteomic changes across varying gestational ages for several pathways which include; coagulation, inflammation, complement activations and immunomodulation [ 13 , 14 ]. Suski et al also observed Complement C3, Factor V and Complement C4-A were associated with gestational age [ 13 ].…”

Section: Resultsmentioning

confidence: 99%

The use of proteomics for blood biomarker research in premature infants: a scoping review

et al. 2021

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Over the last decade, the use of proteomics in the setting of prematurity has increased and has enabled researchers to successfully identify biomarkers for an array of associated morbidities. The objective of this scoping review was to identify the existing literature, as well as any knowledge gaps related to proteomic biomarker discoveries in the setting of prematurity. A scoping review was conducted using PubMed, Embase and Medline databases following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The study selection process yielded a total of 700 records, of which 13 studies were included in this review. Most studies used a tandem Mass Spectrometry (MS/MS) proteomics approach to identify key biomarkers. The corresponding studies identified proteins associated with retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), late onset sepsis (LOS) and gestational age. This scoping review demonstrates the limited use of proteomics to identify biomarkers associated with severe complications of prematurity. Further research is warranted to identify biomarkers of other important morbidities associated with prematurity, such as intraventricular haemorrhage (IVH) and cerebral palsy, and to investigate the mechanisms associated with these outcomes.

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“…A formal sample size calculation was not performed so as to allow the realization of a hypothesis generating study. The approximate sample size was based on the calculations for the main study [7]. Briefly, the basic goal of the main project was to compare protein abundance levels between groups with a different degree of maturity.…”

Section: Methodsmentioning

confidence: 99%

“…In our previous publications, we described the comparison between abundances of all plasma proteins from prematurely born children with different gestational ages, both from cord blood as well as at the 36th postmenstrual week (36 PMA) [7–9]. The articles presented that proteome differences are highly gestational age-dependent.…”

Section: Introductionmentioning

confidence: 99%

“…In this study, we aimed to identify potential BPD plasma biomarkers and to provide a more molecular-based understanding of BPD, by comparing a proteome profile at two time points (at birth and at the 36 PMA) in groups of infants with and without BPD. However, according to our previous observations, the level of prematurity has a fundamental influence on the plasma protein quantitative changes [7–9]. Therefore, we performed a standardization of the obtained results for the gestational age.…”

Section: Introductionmentioning

confidence: 99%

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Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia

et al. 2019

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Background In this study, we aimed to analyze differences in plasma protein abundances between infants with and without bronchopulmonary dysplasia (BPD), to add new insights into a better understanding of the pathogenesis of this disease. Methods Cord and peripheral blood of neonates (≤ 30 weeks gestational age) was drawn at birth and at the 36th postmenstrual week (36 PMA), respectively. Blood samples were retrospectively subdivided into BPD(+) and BPD(−) groups, according to the development of BPD. Results Children with BPD were characterized by decreased afamin, gelsolin and carboxypeptidase N subunit 2 levels in cord blood, and decreased galectin-3 binding protein and hemoglobin subunit gamma-1 levels, as well as an increased serotransferrin abundance in plasma at the 36 PMA. Conclusions BPD development is associated with the plasma proteome changes in preterm infants, adding further evidence for the possible involvement of disturbances in vitamin E availability and impaired immunological processes in the progression of prematurity pulmonary complications. Moreover, it also points to the differences in proteins related to infection resistance and maintaining an adequate level of hematocrit in infants diagnosed with BPD.

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Plasma proteome changes in cord blood samples from preterm infants

Abstract: Plasma proteome analysis revealed numerous gestation-age-dependent protein abundance differences between term and preterm infants, which highlight key dysregulated pathways and potential new protein treatment targets.

Cited by 12 publications

References 71 publications

Composition and origin of lung fluid proteome in premature infants and relationship to respiratory outcome

Composition and origin of lung fluid proteome in premature infants and relationship to respiratory outcome

The use of proteomics for blood biomarker research in premature infants: a scoping review

Comparative two time-point proteome analysis of the plasma from preterm infants with and without bronchopulmonary dysplasia

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