AUTHOR=Canul-Euan Arturo Alejandro , Zúñiga-González Gibran , Palacios-Luna Janelly Estefania , Maida-Claros Rolando , Díaz Néstor Fabián , Saltigeral-Tigeral Patricia , Karina García-May Perla , Díaz-Ruiz Oscar , Flores-Herrera Héctor 

TITLE=Increased Levels of Plasma Extracellular Heat-Shock Proteins 60 and 70 kDa Characterized Early-Onset Neonatal Sepsis

JOURNAL=Frontiers in Pediatrics

VOLUME=9

YEAR=2021

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2021.740274

DOI=10.3389/fped.2021.740274

ISSN=2296-2360

ABSTRACT=<p><bold>Background:</bold> Extracellular heat-shock proteins (<italic>e</italic>Hsp) are highly conserved molecules that play an important role in inflammatory diseases and have been quantified in plasma from patients with infectious diseases, including sepsis. There is a constant search for dependable biochemical markers that, in combination with conventional methods, could deliver a prompt and reliable diagnosis of early-onset neonatal sepsis.</p><p><bold>Objective:</bold> We sought to assess the level of <italic>e</italic>Hsp-27, <italic>e</italic>Hsp-60, <italic>e</italic>Hsp-70, and tumor necrosis factor-alpha (TNFα) in plasma of healthy neonates at term and infants with early-onset neonatal sepsis.</p><p><bold>Methods:</bold> This study included 34 newborns that were classified as healthy neonates at term (blood samples from the umbilical cord, <italic>n</italic> = 23) or infants with early-onset neonatal sepsis (blood samples obtained from umbilical artery by standard sterile procedures before starting a systemic antibiotic intervention, <italic>n</italic> = 11). All blood samples were centrifuged, and the plasma recovered to determine <italic>e</italic>Hsp-27, <italic>e</italic>Hsp-60, <italic>e</italic>Hsp-70, and TNFα levels by ELISA.</p><p><bold>Results:</bold> Our results indicate that the level of <italic>e</italic>Hsp-27 in healthy neonates at term was 0.045 ± 0.024 pg/ml. This value decreased 2.5-fold in infants with early-onset neonate sepsis (0.019 ± 0.006 pg/ml, <italic>p</italic> = 0.004). In contrast, the levels of <italic>e</italic>Hsp-60 and <italic>e</italic>Hsp-70 in healthy neonates at term were 13.69 ± 5.3 and 4.03 ± 2.6 pg/ml, respectively. These protein levels increased significantly 1.8- and 1.9-fold in the plasma of infants with early-onset neonatal sepsis (<italic>p</italic> ≤ 0.001). The level of TNFα in healthy neonates at term was 2.94 ± 0.46 pg/ml, with a 3.0-fold increase in infants with early-onset neonatal sepsis (8.96 ± 0.72 pm/ml, <italic>p</italic> ≤ 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of <italic>e</italic>Hsp compared with that of C-reactive protein were 73.3, 60.0, 47.8, and 33.3%, respectively.</p><p><bold>Conclusion:</bold> This study demonstrated a consistent increase of <italic>e</italic>Hsp-60 and <italic>e</italic>Hsp-70 in the plasma of infants diagnosed with early-onset neonatal sepsis. These proteins showed higher sensitivity and specificity than C-reactive protein and blood culture test.</p>