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

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.

Saliva as a sampling matrix for therapeutic drug monitoring of gentamicin in neonates: A prospective population pharmacokinetic and simulation study

“…However, the low sample volumes may be due to inadequate sampling technique or insufficient saliva production by subjects, especially with premature neonates. Future studies may employ a different sampling strategy to ensure that an adequate volume of saliva is drawn, such as use of a different swab or cutting the saturated end of the swab 30,31 . Saliva secretion was not stimulated with citric acid as it substantially increases the burden of saliva collection.…”

“…(PMA) correlated negatively with both k 13 and k 30 . Simulations demonstrated that TDM with four saliva samples was accurate in 81% of the simulated cases versus 94% when performed with two plasma samples and 87% when performed with one plasma sample.…”

Basics for the potential use of saliva to evaluate stress, inflammation, immune system, and redox homeostasis in pigs

“…The mechanisms which are responsible for the presence of APPs in saliva are still to be elucidated. However, in pigs as in other species such as dogs or humans, some APPs like CRP were significantly correlated in saliva and serum; and recently a transport process for CRP from blood to saliva in humans has been described [ 48 ].…”

Comparison of C-Reactive Protein in Dried Blood Spots and Saliva of Healthy Adolescents

“…Consequently, validating the diagnostic potential of biomarker levels in saliva is of great interest. To date, numerous studies comparing salivary CRP (sCRP) with blood CRP levels have found moderate to strong correlations in neonates, adolescents, and adults ( 30 – 34 ). However, Dillon and colleagues ( 35 ) could not establish any association between both parameters in healthy adults, and an article reviewing correlations reported by 14 studies concludes that the overall association of sCRP with serum CRP is moderate ( 36 ).…”