Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Abstract

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P-and E-selectins, interleukin 2 soluble receptor ␣, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18

“…Increased IL-18 expression has been demonstrated in premature neonates with brain injury (25) or sepsis (26) and NEC (27). Intriguingly, gut IL-17A mRNA was increased in experimental NEC in baboons (28), and recently IL-17A protein was shown to impair enterocyte tight junctions, increase enterocyte apoptosis, and reduce enterocyte proliferation leading to NEC in mice (29), highlighting the potential role of the IL-18/IL-17A axis in other neonatal inflammatory diseases.…”

Nanocellulose-Based Biosensors: Design, Preparation, and Activity of Peptide-Linked Cotton Cellulose Nanocrystals Having Fluorimetric and Colorimetric Elastase Detection Sensitivity

“…HNE has been shown to be a specific marker for psoriasis [45], an early prognostic marker of acute pancreatitis [46] and of cardiovascular events in patients with angina pectoris [47]. HNE has also been documented as a biomarker in neonatal sepsis [48] and septic shock [49], and has been suggested as a biomarker for newborns with cystic fibrosis transmembrane conductance regulator related metabolic syndrome (CRMS), a form of cystic fibrosis (CF) that does not meet the diagnostic criteria for clinically diagnosed CF [50]. Thus, the prevalence of HNE in some chronic inflammatory diseases suggests its use as an analyte for diagnosis and treatment.…”

Neonatal Sepsis: past, present and future; a review article

“…40 Molecular tools (16S-rRNA) demonstrate that the diversity of microbial agents of intra-amniotic infection exceeds what is suspected clinically or is documented by cultures. The resulting inflammatory process has the potential to damage the fetus in utero.…”