Supervisors info:
Σουλτάνα Σιαχανίδου, Αναπληρώτρια Καθηγήτρια , Ιατρική, ΕΚΠΑ
Γεώργιος Βαϊόπουλος, Ομότιμος Καθηγητής, Ιατρική, ΕΚΠΑ
Μιχάλης Κουτσιλιέρης, Καθηγητής , Ιατρική, ΕΚΠΑ
Summary:
Infections remain one of the leading causes of morbidity and mortality in neonatal age and may also cause severe long-term consequences. Early diagnosis isn’t always easy and until now, no laboratory biomarker is ideal. Paraoxonase-1 (PON-1) is an A-esterase secreted mainly by the liver with antioxidant, anti-inflammatory and antimicrobial properties. The activity of PON-1 in the serum is expressed through the hydrolysis of paraoxon (paraoxonase) or hydrolysis of phenylacetate (arylesterase). Previous studies in animals and adults have shown that the levels of PON-1 are lower in the acute phase of infection. Serum amyloid A (SAA) is an acute phase protein produced mainly by liver cells in response to cytokines. Previous studies have shown that SAA’s levels increase during the infection, but for neonates the studies are few and with contradictory results.
Purpose. The objective of this study was 1) the evaluation of the levels of paraoxonase, arylesterase and SAA during the acute phase and in recovery of neonatal infection, 2) the correlation with CRP, WBC, cytokines (IL-1a, IL-1b, IL-6, TNF-a) and HDL and 3) the examination of their diagnostic value.
Materials and Methods. The study population consisted of 41 full-term neonates with clinical signs and symptoms of sepsis and 34 neonates, of similar postnatal age and gender distribution to those of infected infants, as controls. Blood samples were drawn in the first 24 hours of admission (acute phase) and 7-10 days following admission (recovery) in patients, and once in controls for the evaluation of WBC, CRP, serum HDL, paraoxonase and arylesterase activity (spectrophotometrically using as substrate paraoxon and phenylacetate respectively), serum amyloid A with nephelometry and serum cytokines (IL-1a, IL-1b, IL-6, TNF-a) with Luminex technology.
Results. The levels of paraoxonase and arylesterase didn’t differ between patients in acute phase (19.02±18.15 U/min/ml and 31.9±16.5 KU/min/ml respectively) and controls (25.5±21.88 U/min/ml and 39.48±17.55 KU/min/ml respectively). Difference wasn’t observed also between the patients in recovery and controls. Serum paraoxonase and arylesterase values were significantly increased in patients in recovery in comparison with the acute phase (p=0.042 and p=0.008 respectively). The levels of serum amyloid A were significantly elevated in patients in the acute phase (149±178 mg/L) in comparison with patients in recovery (4.13±1.21 mg/L, p=0.0001) and controls (4.45±3.77 mg/L, p=0.0001), and correlated positively with CRP (rs=0.77, p=0.0001), WBC (rs=0.498, p=0.002), and IL-6 (rs=0.492, p=0.003). According to the results of ROC analysis, serum amyloid A is an accurate biomarker for the diagnosis of neonatal infection in total (AUC=0.947 p=0.0001) and also for the diagnosis of culture positive infections (AUC=0.894, p=0.0001).
Conclusion. Serum amyloid A can be used in daily routine for the diagnosis of neonatal infections. As for paraoxonase and arylesterase, they are not accurate diagnostic markers but they could be used for the monitoring of infection.
Keywords:
Neonatal Infections, Paraoxonase-1, Paraoxonase, Arylesterase, Serum amyloid A
