Quantitative Measurement of Monocyte HLA-DR Expression in the Identification of Early-Onset Neonatal Infection

Abstract

Background: This study aimed to evaluate the diagnostic utilities of monocyte HLA-DR as an infection marker in the identification of early-onset clinical infection and pneumonia in newborn infants. Methods: Term newborns in whom infection was suspected when they were <72 h of age were eligible for enrollment in the study. C-reactive protein (CRP), monocyte HLA-DR and neutrophil CD64 expressions were quantitatively measured at the time of sepsis evaluation (0 h) and 24 h afterwards by flow cytometry and standard laboratory method. Results: A total of 288 infants with suspected sepsis were investigated, and 93 were found to be clinically infected. There were no significant differences in monocyte HLA-DR expression between the infected, non-infected and control groups at 0 h (median (interquartile range): 13,986 (10,994–18,544), 14,234 (12,045–17,474) and 18,441 (14,250–21,537) antibody phycoerythrin (PE) molecules bound/cell), and between infected and non-infected infants at 24 h (median (interquartile range): 17,772 (12,933–25,167) and 19,406 (14,885–24,225) antibody PE molecules bound/cell). The areas under the receiver operating characteristics (ROC) curves for HLA-DR, CD64 and CRP were 0.52–0.54, 0.88–0.94 and 0.75–0.77, respectively. We were unable to determine an optimal cutoff value for HLA-DR, as the diagnostic utilities of any cutoff point on the ROC curves were unable to satisfy the criteria (i.e. sensitivity and specificity ≧80%) for consideration as an useful diagnostic marker of infection. Conclusions: Our findings did not support the use of monocyte HLA-DR alone or in combination with other infection markers in the diagnosis of early-onset clinical infection and pneumonia in term newborns.

Early Diagnosis of Sepsis Through Sepsis Markers and Sepsis Index Through Flow Cytometry Technology

“…In another study, Ng et al demonstrated no significant difference between infected and non-infected or control groups for mHLA-DR expression [31]. In our study, a trend analysis of mHLA-DR indicated that mHLA-DR was significantly downregulated in non-survivors only at a later stage.…”

An Update on the Use of C-Reactive Protein in Early-Onset Neonatal Sepsis: Current Insights and New Tasks

“…The sensitivity and specificity of CD11b for diagnosing early-onset neonatal sepsis are 86–100 and 100%, respectively [5,59]. CD64 has a sensitivity ranging between 78 and 96% and a NPV between 89 and 97% [70,71]. Though promising, estimation of cell surface markers is limited by the need for sophisticated equipment and the need to process blood samples rapidly before neutrophils die from apoptosis or the surface antigens are downregulated [72].…”

Ratio of neutrophilic CD64 and monocytic HLA‐DR: A novel parameter in diagnosis and prognostication of neonatal sepsis

“…Although mHLA-DR was downregulated in non-survivors of sepsis at the very onset, nonsurvivors were significantly younger than survivors, but no adjustment for multivariate analysis had been done (18), whereas variation of mHLA-DR with postnatal age is documented (25). On the other hand, Ng et al demonstrated no significant difference in mHLA-DR expression between infected and non-infected or control groups (16). In this study, a trend analysis of mHLA-DR indicated that mHLA-DR was significantly downregulated in non-survivors only at a later stage, i.e., days 4-6 (Supporting Information content 4 and Fig.…”

“…On the other hand, decreased expression of HLA-DR molecules on circulating monocytes has been associated with an anti-inflammatory immune response, referred to as "immunoparalysis" in sepsis (14,15). While the diagnostic significance of HLA-DR is limited (16), a decrease in HLA-DR on monocytes has been associated with deaths in adults (17) and newborn infections (18,19).…”