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Article

Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis

1
Center for Health and Bioresources, Competence Unit Molecular Diagnostics, Austrian Institute of Technology (AIT) GmbH, Giefinggasse 4, 1210 Vienna, Austria
2
Division of Neonatology, Paediatric Intensive Care & Neuropaediatrics, Department of Paediatrics and Adolescent Medicine, Comprehensive Center for Paediatrics, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
3
School of Clinical Dentistry, University of Sheffield, Broomhall, Sheffield S10 2TG, UK
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Pharmaceutics 2021, 13(2), 256; https://doi.org/10.3390/pharmaceutics13020256
Submission received: 22 December 2020 / Revised: 31 January 2021 / Accepted: 4 February 2021 / Published: 12 February 2021
(This article belongs to the Special Issue Biological Barriers in Health and Disease)

Abstract

C-reactive protein (CRP) is a commonly used serum biomarker for detecting sepsis in neonates. After the onset of sepsis, serial measurements are necessary to monitor disease progression; therefore, a non-invasive detection method is beneficial for neonatal well-being. While some studies have shown a correlation between serum and salivary CRP levels in septic neonates, the causal link behind this correlation remains unclear. To investigate this relationship, CRP was examined in serum and saliva samples from 18 septic neonates and compared with saliva samples from 22 healthy neonates. While the measured blood and saliva concentrations of the septic neonates varied individually, a correlation of CRP levels between serum and saliva samples was observed over time. To clarify the presence of active transport of CRP across the blood–salivary barrier (BSB), transport studies were performed with CRP using in vitro models of oral mucosa and submandibular salivary gland epithelium. The results showed enhanced transport toward saliva in both models, supporting the clinical relevance for salivary CRP as a biomarker. Furthermore, CRP regulated the expression of the receptor for advanced glycation end products (RAGE) and the addition of soluble RAGE during the transport studies indicated a RAGE-dependent transport process for CRP from blood to saliva.
Keywords: neonatology; saliva diagnostics; infectious disease; immunology; neonatal sepsis; TR146; HTB-41 (A-253) neonatology; saliva diagnostics; infectious disease; immunology; neonatal sepsis; TR146; HTB-41 (A-253)
Graphical Abstract

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MDPI and ACS Style

Lin, G.C.; Küng, E.; Smajlhodzic, M.; Domazet, S.; Friedl, H.P.; Angerer, J.; Wisgrill, L.; Berger, A.; Bingle, L.; Peham, J.R.; et al. Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis. Pharmaceutics 2021, 13, 256. https://doi.org/10.3390/pharmaceutics13020256

AMA Style

Lin GC, Küng E, Smajlhodzic M, Domazet S, Friedl HP, Angerer J, Wisgrill L, Berger A, Bingle L, Peham JR, et al. Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis. Pharmaceutics. 2021; 13(2):256. https://doi.org/10.3390/pharmaceutics13020256

Chicago/Turabian Style

Lin, Grace C., Erik Küng, Merima Smajlhodzic, Sandra Domazet, Heinz P. Friedl, Joachim Angerer, Lukas Wisgrill, Angelika Berger, Lynne Bingle, Johannes R. Peham, and et al. 2021. "Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis" Pharmaceutics 13, no. 2: 256. https://doi.org/10.3390/pharmaceutics13020256

APA Style

Lin, G. C., Küng, E., Smajlhodzic, M., Domazet, S., Friedl, H. P., Angerer, J., Wisgrill, L., Berger, A., Bingle, L., Peham, J. R., & Neuhaus, W. (2021). Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis. Pharmaceutics, 13(2), 256. https://doi.org/10.3390/pharmaceutics13020256

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