J Pediatr Infect Dis 2023; 18(04): 193-198
DOI: 10.1055/s-0043-1767814
Original Article

Evaluation of Changes in Leukocyte Surface Markers in the Early Diagnosis of Late-Onset Neonatal Sepsis

1   Department of Pediatrics, Sivas Public Hospital, Sivas, Türkiye
,
2   Department of Pediatrics and Neonatal Critical Care, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak, Türkiye
,
3   Department of Immunology, Faculty of Medicine, Zonguldak Bulent Ecevit University, Zonguldak, Türkiye
› Author Affiliations
Funding This study was supported by Zonguldak Bülent Ecevit University Scientific Research Scholarship.

Abstract

Objective This study aimed to evaluate the cluster of differentiation (CD)64, CD16, CD11b, CD63 human leukocyte antigen-DR (HLA-DR), and CD62L leukocyte surface marker abnormalities using flow cytometry in the early diagnosis of late-onset neonatal sepsis.

Methods Forty-four neonates were included in this study. Of them, 22 neonates with clinical late-onset neonatal sepsis were included in the study group, and the remaining 22 neonates without sepsis were considered the control group. Complete sepsis screening was performed. Additionally, monocyte and neutrophil surfaces marker were examined using flow cytometry.

Results The expression of the leukocyte surface markers CD16 and CD64 on monocytes and neutrophils was significantly higher in the study group than in the control group (p < 0.05), while the CD63, CD62L, CD11b, and HLA-DR levels were similar to those in the control group (p > 0.05). Furthermore, receiver operating characteristic curve analysis indicated that neutrophil CD64 (nCD64) is a diagnostic marker for neonatal sepsis, with an area under the curve of 0.901. The CD64 and CD16, which are the respective leukocyte surface markers on neutrophils and monocytes, are useful tests in the early diagnosis of late-onset neonatal sepsis.

Conclusion In addition to acute phase proteins, cell surface antigens such as CD16 and more specifically CD64 should be used in routine investigations for the early diagnosis of late-onset neonatal sepsis. Such use in combination with acute phase reactants can improve diagnostic accuracy.



Publication History

Received: 27 November 2022

Accepted: 25 February 2023

Article published online:
04 April 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Mohsen AH, Kamel BA. Predictive values for procalcitonin in the diagnosis of neonatal sepsis. Electron Physician 2015; 7 (04) 1190-1195
  • 2 Ng PC, Lam HS. Biomarkers for late-onset neonatal sepsis: cytokines and beyond. Clin Perinatol 2010; 37 (03) 599-610
  • 3 Du J, Li L, Dou Y, Li P, Chen R, Liu H. Diagnostic utility of neutrophil CD64 as a marker for early-onset sepsis in preterm neonates. PLoS One 2014; 9 (07) e102647
  • 4 Chouhan S, Hansa J, Pradhan S. Early diagnosis of sepsis through sepsis markers and sepsis index through flow cytometry technology. Asian J Pharm Clin Res 2017; 10 (11) 145-148
  • 5 Wang K, Bhandari V, Chepustanova S. et al. Which biomarkers reveal neonatal sepsis?. PLoS One 2013; 8 (12) e82700
  • 6 Shane AL, Sánchez PJ, Stoll BJ. Neonatal sepsis. Lancet 2017; 390 (10104): 1770-1780
  • 7 Rohil A, Dutta S, Varma N, Sachdev MS, Bansal A, Kumar P. Cell-surface biomarkers, c-reactive protein and haematological parameters for diagnosing late onset sepsis in pre-term neonates. J Trop Pediatr 2021; 67 (01) fmab016
  • 8 Kafetzis DA, Tigani GS, Costalos C. Immunologic markers in the neonatal period: diagnostic value and accuracy in infection. Expert Rev Mol Diagn 2005; 5 (02) 231-239
  • 9 Heo JS. Neutrophil CD11b as a promising marker for early detection of neonatal sepsis. Clin Exp Pediatr 2021; 64 (01) 28-30
  • 10 Ng PC, Lam HS. Diagnostic markers for neonatal sepsis. Curr Opin Pediatr 2006; 18 (02) 125-131
  • 11 Boumiza R, Debard AL, Monneret G. The basophil activation test by flow cytometry: recent developments in clinical studies, standardization and emerging perspectives. Clin Mol Allergy 2005; 3: 9
  • 12 European Medicines Agency (EMA). Report on the Expert Meeting on Neonatal and Paediatric Sepsis. London: 2010. Accessed March 17, 2023 at: https://www.ema.europa.eu/en/documents/report/reportexpert-meeting-neonatal-paediatric-sepsis_en.pdf
  • 13 Genel F, Atlihan F, Gulez N. et al. Evaluation of adhesion molecules CD64, CD11b and CD62L in neutrophils and monocytes of peripheral blood for early diagnosis of neonatal infection. World J Pediatr 2012; 8 (01) 72-75
  • 14 Skirecki T, Mikaszewska-Sokolewicz M, Hoser G, Zielińska-Borkowska U. The early expression of HLA-DR and CD64 myeloid markers is specifically compartmentalized in the blood and lungs of patients with septic shock. Mediators Inflamm 2016; 2016: 3074902
  • 15 Rello J, Valenzuela-Sánchez F, Ruiz-Rodriguez M, Moyano S. Sepsis: a review of advances in management. Adv Ther 2017; 34 (11) 2393-2411
  • 16 Genel F, Atlihan F, Ozsu E, Ozbek E. Monocyte HLA-DR expression as predictor of poor outcome in neonates with late onset neonatal sepsis. J Infect 2010; 60 (03) 224-228
  • 17 Kanakoudi-Tsakalidou F, Debonera F, Drossou-Agakidou V. et al. Flow cytometric measurement of HLA-DR expression on circulating monocytes in healthy and sick neonates using monocyte negative selection. Clin Exp Immunol 2001; 123 (03) 402-407
  • 18 Ng PC, Li G, Chui KM. et al. Quantitative measurement of monocyte HLA-DR expression in the identification of early-onset neonatal infection. Biol Neonate 2006; 89 (02) 75-81
  • 19 Hegge I, Niepel F, Lange A, Vogelgesang A, Heckmann M, Ruhnau J. Functional analysis of granulocyte and monocyte subpopulations in neonates. Mol Cell Pediatr 2019; 6 (01) 5
  • 20 Seidelin JB, Nielsen OH, Strøm J. Soluble L-selectin levels predict survival in sepsis. Intensive Care Med 2002; 28 (11) 1613-1618
  • 21 Lakschevitz FS, Hassanpour S, Rubin A, Fine N, Sun C, Glogauer M. Identification of neutrophil surface marker changes in health and inflammation using high-throughput screening flow cytometry. Exp Cell Res 2016; 342 (02) 200-209 [Internet]
  • 22 Im Y, Yoo H, Ko RE, Lee JY, Park J, Jeon K. Exosomal CD63 in critically ill patients with sepsis. Sci Rep 2021; 11 (01) 20300
  • 23 Hoffmann JJML. Neutrophil CD64: a diagnostic marker for infection and sepsis. Clin Chem Lab Med 2009; 47 (08) 903-916
  • 24 Hsu KH, Chan MC, Wang JM, Lin LY, Wu CL. Comparison of Fcγ receptor expression on neutrophils with procalcitonin for the diagnosis of sepsis in critically ill patients. Respirology 2011; 16 (01) 152-160
  • 25 Ng PC, Li K, Wong RPO, Chui KM, Wong E, Fok TF. Neutrophil CD64 expression: a sensitive diagnostic marker for late-onset nosocomial infection in very low birthweight infants. Pediatr Res 2002; 51 (03) 296-303
  • 26 Naeim F. Principles of Immunophenotyping. Hematopathology 2008: 27-55
  • 27 El-Gamal Y, Heshmat NM, Shehab A, Hasaneen AF. Diagnostic value of CD14+ CD16+ monocytes in neonatal sepsis. J Allergy Clin Immunol 2004; 2 (01) 16-26
  • 28 Shah BA, Padbury JF. Neonatal sepsis: an old problem with new insights. Virulence 2014; 5 (01) 170-178
  • 29 El Shimi MS, Abou Shady NM, Hamed GM, Shedeed NS, Mostafa G. Significance of neutrophilic CD64 as an early marker for detection of neonatal sepsis and prediction of disease outcome. J Matern Fetal Neonatal Med 2017; 30 (14) 1709-1714
  • 30 Hirsh M, Mahamid E, Bashenko Y, Hirsh I, Krausz MM. Overexpression of the high-affinity Fcgamma receptor (CD64) is associated with leukocyte dysfunction in sepsis. Shock 2001; 16 (02) 102-108
  • 31 Adib M, Navaei F, Oreizi F, Saheb-fosoul F, Ostadi V. Evaluation of CD64 expression on peripheral blood neutrophils for early detection of neonatal sepsis. Iran J Immunol 2006; 3 (01) 9-14
  • 32 Streimish I, Bizzarro M, Northrup V. et al. Neutrophil CD64 with hematologic criteria for diagnosis of neonatal sepsis. Am J Perinatol 2014; 31 (01) 21-30
  • 33 Kipfmueller F, Schneider J, Prusseit J. et al. Role of neutrophil CD64 index as a screening marker for late-onset sepsis in very low birth weight infants. PLoS One 2015; 10 (04) e0124634
  • 34 Laıla MY, Abdel Hamead M, Hosny MA. CD64 and CD11b versus conventional bacteriological methods in early detection of bacterial neonatal sepsis. Med J Cairo Univ 2018; 86 (07) 3579-3587
  • 35 Nuutila J, Jalava-Karvinen P, Hohenthal U. et al. Comparison of degranulation of easily mobilizable intracellular granules by human phagocytes in healthy subjects and patients with infectious diseases. Hum Immunol 2009; 70 (10) 813-819
  • 36 Wagner C, Deppisch R, Denefleh B, Hug F, Andrassy K, Hänsch GM. Expression patterns of the lipopolysaccharide receptor CD14, and the FCgamma receptors CD16 and CD64 on polymorphonuclear neutrophils: data from patients with severe bacterial infections and lipopolysaccharide-exposed cells. Shock 2003; 19 (01) 5-12
  • 37 Aydin M, Barut S, Akbulut HH, Ucar S, Orman A. Application of flow cytometry in the early diagnosis of neonatal sepsis. Ann Clin Lab Sci 2017; 47 (02) 184-190
  • 38 Nupponen I, Andersson S, Järvenpää AL, Kautiainen H, Repo H. Neutrophil CD11b expression and circulating interleukin-8 as diagnostic markers for early-onset neonatal sepsis. Pediatrics 2001; 108 (01) E12
  • 39 Weinschenk NP, Farina A, Bianchi DW. Premature infants respond to early-onset and late-onset sepsis with leukocyte activation. J Pediatr 2000; 137 (03) 345-350