Abstract
Background: Extracellular heat-shock proteins (eHsp) 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.Objective: We sought to assess the level of eHsp-27, eHsp-60, eHsp-70, and tumor necrosis factor-alpha (TNFα) in plasma of healthy neonates at term and infants with early-onset neonatal sepsis.Methods: This study included 34 newborns that were classified as healthy neonates at term (blood samples from the umbilical cord, n = 23) or infants with early-onset neonatal sepsis (blood samples obtained from umbilical artery by standard sterile procedures before starting a systemic antibiotic intervention, n = 11). All blood samples were centrifuged, and the plasma recovered to determine eHsp-27, eHsp-60, eHsp-70, and TNFα levels by ELISA.Results: Our results indicate that the level of eHsp-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, p = 0.004). In contrast, the levels of eHsp-60 and eHsp-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 (p ≤ 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, p ≤ 0.001). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of eHsp compared with that of C-reactive protein were 73.3, 60.0, 47.8, and 33.3%, respectively.Conclusion: This study demonstrated a consistent increase of eHsp-60 and eHsp-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.
Highlights
Extracellular heat-shock proteins are highly conserved molecules that regulate cellular homeostasis [1, 2], proliferation, and differentiation of the professional immune system cells and are modulated by temperature [3–5]
We showed that infants with early-onset neonatal sepsis presented increased levels of Extracellular heat-shock proteins (eHsp)-60 and eHsp-70 that are correlated with an increment in TNFα (Table 3), supporting previous evidence reported by our group and replicating previous reports [46, 51]
Our findings provide new evidence and support previous results showing that infants with early-onset neonatal sepsis with positive blood culture for E. coli, S. epidermidis, and S. dysgalactiae display marked increase levels of eHsp-60, eHsp-70, and TNFα in plasma
Summary
Extracellular heat-shock proteins (eHsp) are highly conserved molecules that regulate cellular homeostasis [1, 2], proliferation, and differentiation of the professional immune system cells and are modulated by temperature [3–5]. EHsp-60 (HSPD1; heat shock protein family D member 1) and eHsp-70 (HSPA1A; heat shock protein family A member 1A) can stimulate pro-inflammatory cytokines [10, 11], whereas eHsp-27 (HSPB1; heat shock protein family B (small) member 1) has an important anti-inflammatory function [12–14]. Their presence has been shown and their levels quantified in serum and plasma of patients with severe trauma [15, 16], chronic obstructive pulmonary disease [17, 18], inflammatory processes induced by multiple sclerosis [19], and sepsis [20, 21]. 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
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