Neutrophil-surface antigens CD11b and CD64 expression: a potential predictor of early-onset neonatal sepsis

Abstract

Background: CD11b, an α subunit of the β2 integrin adhesion molecule, and CD64, the high affinity Fcγ receptor I, are specific neutrophil-surface antigens activated in response to systemic inflammation and, hence, they might potentially help identifying neonatal infections. Objective: We sought to evaluate the time course of expression and diagnostic and prognostic utility of CD11b and CD64 in early-onset sepsis in the suspected newborn. Methods: Sixty newborn infants (28-40 weeks gestation) with antenatal risk factors for sepsis were enrolled and subjected to sepsis work-up including complete blood count, quantification of serum C reactive protein (CRP) and flow cytometric analysis of CD11b and CD64 in cord blood (0 h). These tests were repeated at 8, 24 and 48 h postnatally. Neonates were defined, retrospectively, in two groups: sepsis and no infection, on basis of clinical observation over their first five postnatal days and sepsis work-up results. Results: A significant enhancement of neutrophil CD11b and CD64 expression was demonstrated in the sepsis group as compared to the non-infected group. CD11b over-expression had an onset at 0 h. Its mean value approached two-fold mean level of non-infected neonates by 8-24 h, and declined thereafter. CD64 rising onset was detectable at 8 h and its mean percentage reached four-fold mean value of the non-infected group at 24 h. At 24 h, an optimal cut-off value for CD11b expression of 35% (sensitivity 80%, and specificity 100%), and for CD64 expression of 17% (sensitivity 88%, and specificity 90.3%) had the best performance for prediction of sepsis. Combined use of both markers at 24 h yielded 90% sensitivity and 95% specificity for sepsis prediction. Sepsis survivors showed significantly lower mean expression for CD11b and CD64 as compared to those with fatal outcome. At 24 h, a cut-off value of 88% expression for CD11b and 50% expression for CD64 predicted mortality with sensitivity and specificity of 100%. Conclusion: Enhanced expression of neutrophil-surface antigens CD11b and CD64 could be a promising tool for prediction and therapeutic decision-making in early-onset sepsis indicating the necessity of initiation of antimicrobial therapy and reduction of its unnecessary use in non-infected neonates even before definitive microbiologic identification.

Keywords: sepsis, neonate, early-onset, neutrophil activation, surface antigen, CD11b, CD64

Egypt J Pediatr Allergy Immunol 2004; 2(2): 90-100