Diagnostic value of CD14+ CD16+ monocytes in neonatal sepsis

Abstract

Background: The majority of monocytes (MO) are strongly positive for CD14 and negative for CD16. The phenotype and function of peripheral blood monocytes change after trauma and during sepsis. CD14+CD16+ monocytes, identified as a minor population of monocytes which constitute a potent phagocytosing and antigen-presenting monocyte subpopulation that expands during acute and chronic infections. Objective: To evaluate monocyte expression of CD14 and CD16 in preterm neonates and to assess it as a possible marker for early diagnosis of neonatal sepsis as the early clinical signs are often insidious and non-specific. Methods: This study was carried out on 45 preterm neonates (1-3 days old ) with a mean gestational age of 34.5 ± 1.03 weeks . They were classified into three groups. Group I included 15 neonates with proven sepsis. Group II included 15 neonates with possible or suspected infection. Group III (control group) included 15 healthy age and sex matched neonates. The neonates with possible infection were followed up. Nine of them developed sepsis later on (proved clinically and by laboratory) and they were considered as patients with early sepsis at the time of admission. History taking and clinical examination were performed as well as laboratory investigations including, complete blood count, blood culture and sensitivity (for patients only), measurement of C-reactive protein (CRP) and CD14 and CD16 expression on monocytes by flow cytometry. Results: The proportion of CD14+ CD16+ MO within all circulating monocytes was significantly higher in patients with proven (75.2±13.1%), early (63.9±17.9%) or possible sepsis (55.1±26.8%) than controls (3.86±2.53%) (p < 0.0001, p < 0.0001, p < 0.001, respecctively). It was higher in neonates with proven than possible sepsis (p > 0.05), whereas it was comparable in the groups of proven and early sepsis (p < 0.05). There was a significant positive correlation between mean fluorescence intensity (MFI) of CD16+ MO and CRP (p < 0.01) and a significant negative correlation between it and the platelet count (p < 0.05) among patients. When neonates with early sepsis were followed up after 48 hours a significant increase in CRP levels and MFI of CD16 expression on monocytes was noted (p < 0.01 for both). The sensitivity and negative predictive value of CD14+ CD16+ MO% and MFI of CD16+ MO were higher than that of CRP. Specificity and positive predictive value of CD14+CD16+ MO% were similar to those of CRP. The cut off point (obtained from the ROC curve) for CD14+ CD16+ MO% was 8.6% and that for MFI of CD16+ MO was 9. Conclusion: The measurement of the percentage of CD14+ CD16+ MO among circulating MO is a promising rapid and sensitive test for early diagnosis of neonatal sepsis and exclusion of infection in neonates with high risk to develop sepsis. NICU costs as well as unnecessary antibiotic use can be thus reduced.

Keywords: CD14, CD16, monocyte, neonate, sepsis

Egypt J Pediatr Allergy Immunol 2004; 2(1): 16-26