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Plasma proteome changes in cord blood samples from preterm infants

Journal of Perinatology volume 38, pages 1182–1189 (2018)Cite this article

Subjects

Abstract

Objective

In the presented study, we aimed to systematically analyze plasma proteomes in cord blood samples from preterm infants stratified by their gestational age to identify proteins and related malfunctioning pathways at birth, possibly contributing to the complications observed among preterm infants.

Study design

Preterm newborns were enrolled of three subgroups with different gestation age: newborns born ≤26 (group 1), between 27 and 28 (group 2) and between 29 and 30 (group 3) weeks of gestation, respectively, and compared to the control group of healthy, full-term newborns in respect to their plasma proteome composition.

Result

Preterm delivery is associated with multiple protein abundance changes in plasma related to a plethora of processes, including inflammation and immunomodulation, coagulation, and complement activation as some key features.

Conclusion

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.

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References

  1. Miles HL, Hofman PL, Cutfield WS. Fetal origins of adult disease: a paediatric perspective. Rev Endocr Metab Disord. 2005;6:261–8.

    Article  PubMed  Google Scholar 

  2. Barker DJ, Osmond C, Golding J, Kuh D, Wadsworth ME. Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ. 1989;298:564–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Barker DJ, Hales CN, Fall CH, Osmond C, Phipps K, Clark PM. Type 2 (non-insulin-dependent) diabetes mellitus, hypertension and hyperlipidaemia (syndrome X): relation to reduced fetal growth. Diabetologia. 1993;36:62–67.

    Article  PubMed  CAS  Google Scholar 

  4. Barker DJ, Winter PD, Osmond C, Margetts B, Simmonds SJ. Weight in infancy and death from ischaemic heart disease. Lancet. 1989;2:577–80.

    Article  PubMed  CAS  Google Scholar 

  5. Candiano G, Dimuccio V, Bruschi M, Santucci L, Gusmano R, Boschetti E, et al. Combinatorial peptide ligand libraries for urine proteome analysis: investigation of different elution systems. Electrophoresis. 2009;30:2405–11.

    Article  PubMed  CAS  Google Scholar 

  6. Fasoli E, Farinazzo A, Sun CJ, Kravchuk AV, Guerrier L, Fortis F, et al. Interaction among proteins and peptide libraries in proteome analysis: pH involvement for a larger capture of species. J Proteom. 2010;73:733–42.

    Article  CAS  Google Scholar 

  7. Gallardo Ó, Ovelleiro D, Gay M, Carrascal M, Abian J. A collection of open source applications for mass spectrometry data mining. Proteomics. 2014;14:2275–9.

    Article  PubMed  CAS  Google Scholar 

  8. Craig R, Beavis RC. TANDEM: matching proteins with tandem mass spectra. Bioinformatics. 2004;20:1466–7.

    Article  PubMed  CAS  Google Scholar 

  9. Eng JK, Jahan TA, Hoopmann MR. Comet: an open-source MS/MS sequence database search tool. Proteomics. 2013;13:22–24.

    Article  PubMed  CAS  Google Scholar 

  10. Shteynberg D, Deutsch EW, Lam H, Eng JK, Sun Z, Tasman N, et al. iProphet: multi-level integrative analysis of shotgun proteomic data improves peptide and protein identification rates and error estimates. Mol Cell Proteom. 2011;10:M111.007690.

    Article  CAS  Google Scholar 

  11. Deutsch EW, Mendoza L, Shteynberg D, Farrah T, Lam H, Tasman N, et al. A guided tour of the trans-proteomic pipeline. Proteomics. 2010;10:1150–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Reiter L, Claassen M, Schrimpf SP, Jovanovic M, Schmidt A, Buhmann JM, et al. Protein identification false discovery rates for very large proteomics data sets generated by tandem mass spectrometry. Mol Cell Proteom. 2009;8:2405–17.

    Article  CAS  Google Scholar 

  13. Taverner T, Karpievitch YV, Polpitiya AD, Brown JN, Dabney AR, Anderson GA, et al. DanteR: an extensible R-based tool for quantitative analysis of -omics data. Bioinformatics. 2012;28:2404–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Vizcaíno JA, Deutsch EW, Wang R, Csordas A, Reisinger F, Ríos D, et al. ProteomeXchange provides globally coordinated proteomics data submission and dissemination. Nat Biotechnol. 2014;32:223–6.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Pickler R, Brown L, McGrath J, Lyon D, Rattican D, Cheng C-Y, et al. Integrated review of cytokines in maternal, cord, and newborn blood: part II-- associations with early infection and increased risk of neurologic damage in preterm infants. Biol Res Nurs. 2010;11:377–86.

    Article  PubMed  CAS  Google Scholar 

  16. Perrone S, Tataranno ML, Stazzoni G, Buonocore G. Biomarkers of oxidative stress in fetal and neonatal diseases. J Matern Fetal Neonatal Med. 2012;25:2575–8.

    Article  PubMed  CAS  Google Scholar 

  17. Tataranno ML, Perrone S, Buonocore G. Plasma biomarkers of oxidative stress in neonatal brain injury. Clin Perinatol. 2015;42:529–39.

    Article  PubMed  Google Scholar 

  18. Chiesa C, Pacifico L, Natale F, Hofer N, Osborn JF, Resch B. Fetal and early neonatal interleukin-6 response. Cytokine. 2015;76:1–12.

    Article  PubMed  CAS  Google Scholar 

  19. Polberger SK, Fex G, Räihä NC. Concentration of twelve plasma proteins at birth in very low birthweight and in term infants. Acta Paediatr Scand. 1990;79:729–36.

    Article  PubMed  CAS  Google Scholar 

  20. Hochepied T, Berger FG, Baumann H, Libert C. Alpha(1)-acid glycoprotein: an acute phase protein with inflammatory and immunomodulating properties. Cytokine Growth Factor Rev. 2003;14:25–34.

    Article  PubMed  CAS  Google Scholar 

  21. Costello MJ, Gewurz H, Siegel JN. Inhibition of neutrophil activation by alpha1-acid glycoprotein. Clin Exp Immunol. 1984;55:465–72.

    PubMed  PubMed Central  CAS  Google Scholar 

  22. Nakamura K, Ito I, Kobayashi M, Herndon DN, Suzuki F. Orosomucoid 1 drives opportunistic infections through the polarization of monocytes to the M2b phenotype. Cytokine. 2015;73:8–15.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Druhan LJ, Lance A, Li S, Price AE, Emerson JT, Baxter SA, et al. Leucine rich α-2 glycoprotein: a novel neutrophil granule protein and modulator of myelopoiesis. PLoS ONE. 2017;12:e0170261.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Shirai R, Hirano F, Ohkura N, Ikeda K, Inoue S. Up-regulation of the expression of leucine-rich alpha(2)-glycoprotein in hepatocytes by the mediators of acute-phase response. Biochem Biophys Res Commun. 2009;382:776–9.

    Article  PubMed  CAS  Google Scholar 

  25. Majek P, Riedelova-Reicheltova Z, Suttnar J, Pecankova K, Cermak J, Dyr JE. Proteome changes in the plasma of myelodysplastic syndrome patients with refractory anemia with excess blasts subtype 2. Dis Markers. 2014;2014:178709.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Kharbanda AB, Rai AJ, Cosme Y, Liu K, Dayan PS. Novel serum and urine markers for pediatric appendicitis. Acad Emerg Med. 2012;19:56–62.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Welters ID, Bing C, Ding C, Leuwer M, Hall AM. Circulating anti-inflammatory adipokines High Molecular Weight Adiponectin and Zinc-α2-glycoprotein (ZAG) are inhibited in early sepsis, but increase with clinical recovery: a pilot study. BMC Anesthesiol. 2014;14:124.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Voegele AF, Jerković L, Wellenzohn B, Eller P, Kronenberg F, Liedl KR, et al. Characterization of the vitamin E-binding properties of human plasma afamin. Biochemistry. 2002;41:14532–8.

    Article  PubMed  CAS  Google Scholar 

  29. Lu C-H, Lin S-T, Chou H-C, Lee Y-R, Chan H-L. Proteomic analysis of retinopathy-related plasma biomarkers in diabetic patients. Arch Biochem Biophys. 2013;529:146–56.

    Article  PubMed  CAS  Google Scholar 

  30. Schleiffenbaum B, Spertini O, Tedder TF. Soluble L-selectin is present in human plasma at high levels and retains functional activity. J Cell Biol. 1992;119:229–38.

    Article  PubMed  CAS  Google Scholar 

  31. Koehne PS, Wagner MH, Willam C, Sonntag J, Bührer C, Obladen M. Soluble intercellular cell adhesion molecule-1 and L-selectin plasma concentrations and response to surfactant in preterm infants. Pediatr Crit Care Med. 2002;3:23–28.

    Article  PubMed  Google Scholar 

  32. Rubin H, Wang ZM, Nickbarg EB, McLarney S, Naidoo N, Schoenberger OL, et al. Cloning, expression, purification, and biological activity of recombinant native and variant human alpha 1-antichymotrypsins. J Biol Chem. 1990;265:1199–207.

    PubMed  CAS  Google Scholar 

  33. van den Berg JP, Westerbeek EAM, van der Klis FRM, Berbers GAM, van Elburg RM. Transplacental transport of IgG antibodies to preterm infants: a review of the literature. Early Hum Dev. 2011;87:67–72.

    Article  PubMed  CAS  Google Scholar 

  34. Källman J, Schollin J, Schalèn C, Erlandsson A, Kihlström E. Impaired phagocytosis and opsonisation towards group B streptococci in preterm neonates. Arch Dis Child Fetal Neonatal Ed. 1998;78:F46–50.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Lippi G, Franchini M, Montagnana M, Guidi GC. Coagulation testing in pediatric patients: the young are not just miniature adults. Semin Thromb Hemost. 2007;33:816–20.

    Article  PubMed  CAS  Google Scholar 

  36. Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, et al. Development of the human coagulation system in the healthy premature infant. Blood. 1988;72:1651–7.

    PubMed  CAS  Google Scholar 

  37. Andrew M, Paes B, Milner R, Johnston M, Mitchell L, Tollefsen DM, et al. Development of the human coagulation system in the full-term infant. Blood. 1987;70:165–72.

    PubMed  CAS  Google Scholar 

  38. Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood. 1992;80:1998–2005.

    PubMed  CAS  Google Scholar 

  39. Andrew M. Developmental hemostasis: relevance to hemostatic problems during childhood. Semin Thromb Hemost. 1995;21:341–56.

    Article  PubMed  CAS  Google Scholar 

  40. Toulon P. Developmental hemostasis: laboratory and clinical implications. Int J Lab Hematol. 2016;38(Suppl 1):66–77.

    Article  PubMed  Google Scholar 

  41. Sottrup-Jensen L. Alpha-macroglobulins: structure, shape, and mechanism of proteinase complex formation. J Biol Chem. 1989;264:11539–42.

    PubMed  CAS  Google Scholar 

  42. Neves D, Estrozi LF, Job V, Gabel F, Schoehn G, Dessen A. Conformational states of a bacterial α2-macroglobulin resemble those of human complement C3. PLoS ONE. 2012;7:e35384.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Meilinger M, Gschwentner C, Burger I, Haumer M, Wahrmann M, Szollar L, et al. Metabolism of activated complement component C3 is mediated by the low density lipoprotein receptor-related protein/alpha(2)-macroglobulin receptor. J Biol Chem. 1999;274:38091–6.

    Article  PubMed  CAS  Google Scholar 

  44. Hoogendoorn H, Toh CH, Nesheim ME, Giles AR. Alpha 2-macroglobulin binds and inhibits activated protein C. Blood. 1991;78:2283–90.

    PubMed  CAS  Google Scholar 

  45. Mitchell L, Piovella F, Ofosu F, Andrew M. Alpha-2-macroglobulin may provide protection from thromboembolic events in antithrombin III-deficient children. Blood. 1991;78:2299–304.

    PubMed  CAS  Google Scholar 

  46. Tolosano E, Fagoonee S, Morello N, Vinchi F, Fiorito V. Heme scavenging and the other facets of hemopexin. Antioxid Redox Signal. 2010;12:305–20.

    Article  PubMed  CAS  Google Scholar 

  47. Lin T, Maita D, Thundivalappil SR, Riley FE, Hambsch J, Van Marter LJ, et al. Hemopexin in severe inflammation and infection: mouse models and human diseases. Crit Care. 2015;19:166.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Christensen RD, Yaish HM. Hemolysis in preterm neonates. Clin Perinatol. 2016;43:233–40.

    Article  PubMed  Google Scholar 

  49. Kaplan M, Muraca M, Hammerman C, Rubaltelli FF, Vilei MT, Vreman HJ, et al. Imbalance between production and conjugation of bilirubin: a fundamental concept in the mechanism of neonatal jaundice. Pediatrics. 2002;110:e47.

    Article  PubMed  Google Scholar 

  50. Watchko JF. Hyperbilirubinemia and bilirubin toxicity in the late preterm infant. Clin Perinatol. 2006;33:839–52.

    Article  PubMed  Google Scholar 

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Acknowledgements

The research leading to these results has received funding from the Polish-Norwegian Research Programme operated by the National Centre for Research and Development under the Norwegian Financial Mechanism 2009–2014 in the frame of Project Contract No Pol-Nor/196065/54/2013. The mass spectrometry measurements have been performed at Center for Medical Genomics OMICRON, Jagiellonian University Medical College.

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Authors and Affiliations

  1. Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland

    Maciej Suski, Józef Madej & Beata Bujak-Giżycka

  2. Department of Neonatology and Intensive Care Warsaw Medical University, Warsaw, Poland

    Renata Bokiniec, Monika Szwarc-Duma & Maria Katarzyna Borszewska-Kornacka

  3. Department of Pediatrics, Jagiellonian University Medical College, Krakow, Poland

    Teofila Książek, Agnieszka Grabowska, Jacek Józef Pietrzyk & Przemko Kwinta

  4. Department of Pediatric Research, Oslo University Hospital, Oslo, Norway

    Cecilie Revhaug, Lars O. Baumbusch & Ola D. Saugstad

  5. University of Oslo, Oslo, Norway

    Cecilie Revhaug & Ola D. Saugstad

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  1. Maciej Suski
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Correspondence to Maciej Suski.

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Suski, M., Bokiniec, R., Szwarc-Duma, M. et al. Plasma proteome changes in cord blood samples from preterm infants. J Perinatol 38, 1182–1189 (2018). https://doi.org/10.1038/s41372-018-0150-7

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