Monocyte CD64 Does Not Enhance Neutrophil CD64 as a Diagnostic Marker in Neonatal Sepsis

To The Editors: We were intrigued by the recent paper that suggested that monocyte CD64 (mCD64) could enhance the ability of neutrophil CD64 (nCD64) as a diagnostic marker for neonatal sepsis, when expressed as median m/n CD64 values.1 As part of our recent investigations into the role of nCD64 as a diagnostic marker for neonatal sepsis,2,3 we had also collected data on mCD64 measurements. Hence, we went back to analyze our mCD64 data to assess whether it would improve our diagnostic abilities. We had 919 episodes of sepsis evaluations with both nCD64 and mCD64 measurements available. Of these 919, 533 episodes were of early-onset sepsis, of which 2 were culture proven. Of 386 episodes of late-onset sepsis, 46 were culture proven. Hence, we had a total of 48 episodes of culture-proven sepsis available for analysis. As we have done previously,2,3 we generated area under the curve (AUC) for receiver operator characteristic curves using nCD64 and mCD64, controlling for birth weight as a predictor. We found similar values for the AUC 0.88 and 0.82 for nCD64 and mCD64, respectively. Combining the two, even when they were correlated, gave similar results; an AUC of 0.88. We also calculated the AUC using the m/nCD64 ratio and obtained a result of 0.83. This value was similar to that of mCD64 alone, but less than that of nCD64 alone. Next, we performed a simple correlation of nCD64 and mCD64, regardless of repeated measurements, and obtained an R = 0.75, P < 0.0001 (Fig. 1). We concluded that mCD64 appeared to have no additional value in predicting culture-proven neonatal sepsis compared with nCD64 measurements. Our results support reports by other investigators where the mCD64 performed on par or below that of nCD64 as a diagnostic marker for neonatal sepsis.4,5 We speculate the differences in our results, compared with the earlier study,1 could be because of the different methodology used for measuring and analyzing mCD64. Our monocyte and neutrophil CD64 values were generated using a different antibody and were derived using an additional isotype control-based index to control for nonspecific fluorescence, often a significant issue for quantitating monocyte surface marker fluorescence. In addition, the differences in the types of microorganisms (which could instigate variable response in the n and/or m CD64 expression) isolated from the neonates at these 2 sites could also be another potential reason for the discrepant results. Additional studies are required to assess the utility, if any, of mCD64 in addition to that of nCD64, in the diagnosis of neonatal sepsis.FIGURE 1: Simple correlation between neutrophil and mCD64, regardless of repeated measurements. R = 0.75; P < 0.0001.Fang-Yong Li, MPH Veronika Shabanova, MPH Yale Center for Analytical Sciences Chao Wang, BS Henry M. Rinder, MD Department of Laboratory Medicine Yale University School of Medicine Vineet Bhandari, MD, DM Division of Perinatal Medicine Department of Pediatrics Yale University School of Medicine New Haven, CT

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