Skip to main content
Top
Published in: European Journal of Pediatrics 10/2013

01-10-2013 | Original Article

CD15s is a potential biomarker of serious bacterial infection in infants admitted to hospital

Authors: Josko Markic, Ana Jeroncic, Denis Polancec, Nada Bosnjak, Anita Markotic, Julije Mestrovic, Vedrana Cikes Culic

Published in: European Journal of Pediatrics | Issue 10/2013

Login to get access

Abstract

Early recognition of serious bacterial infection (SBI) in children is essential for better treatment outcome. Flow cytometry analysis of neutrophil surface molecules has been more frequently utilized as a tool for diagnosis of infection. The infants (n = 105) under 6 months of age presenting to the pediatric emergency department with fever without apparent source who were hospitalized with suspicion of having SBI were enrolled in this prospective study. Sixty-nine infants were included into the training pool and were classified into bacterial or viral infection group. Validation pool consisted of 36 infants. The values of white blood cells counts, absolute neutrophil count (ANC), C-reactive protein (CRP), procalcitonin (PCT), neutrophil CD11b, CD15s and CD64 expression, and the percentage (%CD15s+) and absolute count (AC-CD15s+) of CD15s+ neutrophils were determined. In infants with SBI, %CD15s+ was 10.5 times more likely to be higher than the cut-off value. ANC, CRP, PCT, CD64, and AC-CD15s+ were also found as useful biomarkers for differentiation between bacterial and viral infection. The best fit multivariate logistic regression model included CRP, PCT, and %CD15s+ as strong predictors of SBI. The model's sensitivity (87 %) and specificity (83 %) indicated high model's accuracy. After validation on independent dataset, model's accuracy maintained high: 86 % sensitivity and 93 % specificity, confirming its reliability and supporting CRP, PCT, and %CD15s+ as real predictors. The findings of this study support assumption made in the literature on significance of CD15s in inflammation processes. Also, this study demonstrated for the first time that CD15s is potentially valuable biomarker of SBI in infants.
Literature
1.
go back to reference Brom J, Koller M, Schluter B, Mullerlange P, Steinau H, Konig W (1995) Expression of the adhesion molecule CD11b and polymerization of actin by polymorphonuclear granulocytes of patients endangered by sepsis. Burns 21:427–431CrossRefPubMed Brom J, Koller M, Schluter B, Mullerlange P, Steinau H, Konig W (1995) Expression of the adhesion molecule CD11b and polymerization of actin by polymorphonuclear granulocytes of patients endangered by sepsis. Burns 21:427–431CrossRefPubMed
2.
go back to reference Chen S, Alon R, Fuhlbrigge R, Springer T (1997) Rolling and transient tethering of leukocytes on antibodies reveal specializations of selectins. Proc Natl Acad Sci U S A 94:3172–3177CrossRefPubMed Chen S, Alon R, Fuhlbrigge R, Springer T (1997) Rolling and transient tethering of leukocytes on antibodies reveal specializations of selectins. Proc Natl Acad Sci U S A 94:3172–3177CrossRefPubMed
3.
go back to reference Cid J, Aguinaco R, Sanchez R, Garcia-Pardo G, Llorente A (2010) Neutrophil CD64 expression as marker of bacterial infection: a systematic review and meta-analysis. J Infect 60:313–319CrossRefPubMed Cid J, Aguinaco R, Sanchez R, Garcia-Pardo G, Llorente A (2010) Neutrophil CD64 expression as marker of bacterial infection: a systematic review and meta-analysis. J Infect 60:313–319CrossRefPubMed
4.
go back to reference Elghetany M, Davis B (2005) Impact of preanalytical variables on granulocytic surface antigen expression: a review. Cytometry B Clin Cytom 65B:1–5CrossRef Elghetany M, Davis B (2005) Impact of preanalytical variables on granulocytic surface antigen expression: a review. Cytometry B Clin Cytom 65B:1–5CrossRef
5.
go back to reference Elghetany M, Lacombe F (2004) Physiologic variations in granulocytic surface antigen expression: impact of age, gender, pregnancy, race, and stress. J Leukoc Biol 75:157–162CrossRefPubMed Elghetany M, Lacombe F (2004) Physiologic variations in granulocytic surface antigen expression: impact of age, gender, pregnancy, race, and stress. J Leukoc Biol 75:157–162CrossRefPubMed
6.
go back to reference Fjaertoft G, Hakansson L, Ewald U, Foucard T, Venge P (1999) Neutrophils from term and preterm newborn infants express the high affinity Fc gamma-receptor I (CD64) during bacterial infections. Pediatr Res 45:871–876CrossRefPubMed Fjaertoft G, Hakansson L, Ewald U, Foucard T, Venge P (1999) Neutrophils from term and preterm newborn infants express the high affinity Fc gamma-receptor I (CD64) during bacterial infections. Pediatr Res 45:871–876CrossRefPubMed
7.
go back to reference Groselj-Grenc M, Ihan A, Pavcnik-Arnol M, Kopitar A, Gmeiner-Stopar T, Derganc M (2009) Neutrophil and monocyte CD64 indexes, lipopolysaccharide-binding protein, procalcitonin and C-reactive protein in sepsis of critically ill neonates and children. Intensive Care Med 35:1950–1958CrossRefPubMed Groselj-Grenc M, Ihan A, Pavcnik-Arnol M, Kopitar A, Gmeiner-Stopar T, Derganc M (2009) Neutrophil and monocyte CD64 indexes, lipopolysaccharide-binding protein, procalcitonin and C-reactive protein in sepsis of critically ill neonates and children. Intensive Care Med 35:1950–1958CrossRefPubMed
8.
go back to reference Hsiao A, Baker M (2005) Fever in the new millennium: a review of recent studies of markers of serious bacterial infection in febrile children. Curr Opin Pediatr 17:56–61CrossRefPubMed Hsiao A, Baker M (2005) Fever in the new millennium: a review of recent studies of markers of serious bacterial infection in febrile children. Curr Opin Pediatr 17:56–61CrossRefPubMed
9.
go back to reference Lacour A, Gervaix A, Zamora S, Vadas L, Lombard P, Dayer J, Suter S (2001) Procalcitonin, IL-6, IL-8, IL-1 receptor antagonist and C-reactive protein as identificators of serious bacterial infections in children with fever without localising signs. Eur J Pediatr 160:95–100CrossRefPubMed Lacour A, Gervaix A, Zamora S, Vadas L, Lombard P, Dayer J, Suter S (2001) Procalcitonin, IL-6, IL-8, IL-1 receptor antagonist and C-reactive protein as identificators of serious bacterial infections in children with fever without localising signs. Eur J Pediatr 160:95–100CrossRefPubMed
10.
go back to reference Lawrence M, Springer T (1993) Neutrophils roll on E-selectin. J Immunol 151:6338–6346PubMed Lawrence M, Springer T (1993) Neutrophils roll on E-selectin. J Immunol 151:6338–6346PubMed
11.
go back to reference Layseca-Espinosa E, Perez-Gonzalez L, Torres-Montes A, Baranda L, de la Fuente H, Rosenstein Y, Gonzalez-Amaro R (2002) Expression of CD64 as a potential marker of neonatal sepsis. Pediatr Allerg Immunol 13:319–327CrossRef Layseca-Espinosa E, Perez-Gonzalez L, Torres-Montes A, Baranda L, de la Fuente H, Rosenstein Y, Gonzalez-Amaro R (2002) Expression of CD64 as a potential marker of neonatal sepsis. Pediatr Allerg Immunol 13:319–327CrossRef
12.
go back to reference Manzano S, Bailey B, Gervaix A, Cousineau J, Delvin E, Girodias J (2011) Markers for bacterial infection in children with fever without source. Arch Dis Child 96:440–446CrossRefPubMed Manzano S, Bailey B, Gervaix A, Cousineau J, Delvin E, Girodias J (2011) Markers for bacterial infection in children with fever without source. Arch Dis Child 96:440–446CrossRefPubMed
13.
go back to reference McGill S, Ahmed N, Hu F, Michel R, Christou N (1996) Shedding of L-selectin as a mechanism for reduced polymorphonuclear neutrophil exudation in patients with the systemic inflammatory response syndrome. Arch Surg 131:1141–1146CrossRefPubMed McGill S, Ahmed N, Hu F, Michel R, Christou N (1996) Shedding of L-selectin as a mechanism for reduced polymorphonuclear neutrophil exudation in patients with the systemic inflammatory response syndrome. Arch Surg 131:1141–1146CrossRefPubMed
14.
go back to reference Mulligan M, Warner R, Rittershaus C, Thomas L, Ryan U, Foreman K, Crouch L, Till G, Ward P (1999) Endothelial targeting and enhanced antiinflammatory effects of complement inhibitors possessing sialyl Lewis(x) moieties. J Immunol 162:4952–4959PubMed Mulligan M, Warner R, Rittershaus C, Thomas L, Ryan U, Foreman K, Crouch L, Till G, Ward P (1999) Endothelial targeting and enhanced antiinflammatory effects of complement inhibitors possessing sialyl Lewis(x) moieties. J Immunol 162:4952–4959PubMed
15.
go back to reference Nakae H, Endo S, Inada K, Takakuwa T, Kasai T (1996) Changes in adhesion molecule levels in sepsis. Res Commun Mol Pathol Pharmacol 91:329–338PubMed Nakae H, Endo S, Inada K, Takakuwa T, Kasai T (1996) Changes in adhesion molecule levels in sepsis. Res Commun Mol Pathol Pharmacol 91:329–338PubMed
16.
17.
go back to reference Ng P, Li K, Wong R, Chui K, Wong E, Fok T (2002) Neutrophil CD64 expression: a sensitive diagnostic marker for late-onset nosocomial infection in very low birthweight infants. Pediatr Res 51:296–303CrossRefPubMed Ng P, Li K, Wong R, Chui K, Wong E, Fok T (2002) Neutrophil CD64 expression: a sensitive diagnostic marker for late-onset nosocomial infection in very low birthweight infants. Pediatr Res 51:296–303CrossRefPubMed
18.
go back to reference Nupponen I, Andersson S, Järvenpää AL, Kautiainen H, Repo H (2001) Neutrophil CD11b expression and circulating interleukin-8 as diagnostic markers for early-onset neonatal sepsis. Pediatrics 108:E12CrossRefPubMed Nupponen I, Andersson S, Järvenpää AL, Kautiainen H, Repo H (2001) Neutrophil CD11b expression and circulating interleukin-8 as diagnostic markers for early-onset neonatal sepsis. Pediatrics 108:E12CrossRefPubMed
19.
go back to reference Olaciregui I, Hernandez U, Munoz J, Emparanza J, Landa J (2009) Markers that predict serious bacterial infection in infants under 3 months of age presenting with fever of unknown origin. Arch Dis Child 94:501–505CrossRefPubMed Olaciregui I, Hernandez U, Munoz J, Emparanza J, Landa J (2009) Markers that predict serious bacterial infection in infants under 3 months of age presenting with fever of unknown origin. Arch Dis Child 94:501–505CrossRefPubMed
20.
go back to reference Pearson G (ed) (2008) Why children die: a pilot study 2006; England (South West, North East and West Midlands), Wales and Northern Ireland. CEMACH, London Pearson G (ed) (2008) Why children die: a pilot study 2006; England (South West, North East and West Midlands), Wales and Northern Ireland. CEMACH, London
21.
go back to reference Rudensky B, Sirota G, Erlichman M, Yinnon A, Schlesinger Y (2008) Neutrophil CD64 expression as a diagnostic marker of bacterial infection in febrile children presenting to a hospital emergency department. Pediatr Emerg Care 24:745–748CrossRefPubMed Rudensky B, Sirota G, Erlichman M, Yinnon A, Schlesinger Y (2008) Neutrophil CD64 expression as a diagnostic marker of bacterial infection in febrile children presenting to a hospital emergency department. Pediatr Emerg Care 24:745–748CrossRefPubMed
22.
go back to reference Sanders S, Barnett A, Correa-Velez I, Coulthard M, Doust J (2008) Systematic review of the diagnostic accuracy of C-reactive protein to detect bacterial infection in nonhospitalized infants and children with fever. J Pediatr 153:570–574CrossRefPubMed Sanders S, Barnett A, Correa-Velez I, Coulthard M, Doust J (2008) Systematic review of the diagnostic accuracy of C-reactive protein to detect bacterial infection in nonhospitalized infants and children with fever. J Pediatr 153:570–574CrossRefPubMed
23.
go back to reference Sengelov H, Kjeldsen L, Diamond M, Springer T, Borregaard N (1993) Subcellular-localization and dynamics of Mac-1 (alpha(M)beta(2)) in human neutrophils. J Clin Invest 92:1467–1476CrossRefPubMed Sengelov H, Kjeldsen L, Diamond M, Springer T, Borregaard N (1993) Subcellular-localization and dynamics of Mac-1 (alpha(M)beta(2)) in human neutrophils. J Clin Invest 92:1467–1476CrossRefPubMed
24.
go back to reference Soni S, Wadhwa N, Kumar R, Faridi M, Sharma S, Chopra A, Singh S (2013) Evaluation of CD64 expression on neutrophils as an early indicator of neonatal sepsis. Pediatr Infect Dis J 32:E33–E37CrossRefPubMed Soni S, Wadhwa N, Kumar R, Faridi M, Sharma S, Chopra A, Singh S (2013) Evaluation of CD64 expression on neutrophils as an early indicator of neonatal sepsis. Pediatr Infect Dis J 32:E33–E37CrossRefPubMed
25.
go back to reference Springer T (1995) Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol 57:827–872CrossRefPubMed Springer T (1995) Traffic signals on endothelium for lymphocyte recirculation and leukocyte emigration. Annu Rev Physiol 57:827–872CrossRefPubMed
26.
go back to reference Tang B, Eslick G, Craig J, McLean A (2007) Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 7:210–217CrossRefPubMed Tang B, Eslick G, Craig J, McLean A (2007) Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis 7:210–217CrossRefPubMed
27.
go back to reference Turunen R, Andersson S, Nupponen I, Kautiainen H, Siitonen S, Repo H (2005) Increased CD11b-density on circulating phagocytes as an early sign of late-onset sepsis in extremely low-birth-weight infants. Pediatr Res 57:270–275CrossRefPubMed Turunen R, Andersson S, Nupponen I, Kautiainen H, Siitonen S, Repo H (2005) Increased CD11b-density on circulating phagocytes as an early sign of late-onset sepsis in extremely low-birth-weight infants. Pediatr Res 57:270–275CrossRefPubMed
28.
go back to reference Vorwerk C, Manias K, Davies F, Coats T (2011) Prediction of severe bacterial infection in children with an emergency department diagnosis of infection. Emerg Med J 28:948–951CrossRefPubMed Vorwerk C, Manias K, Davies F, Coats T (2011) Prediction of severe bacterial infection in children with an emergency department diagnosis of infection. Emerg Med J 28:948–951CrossRefPubMed
29.
go back to reference Weirich E, Rabin R, Maldonado Y, Benitz W, Modler S, Herzenberg L (1998) Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal infection. J Pediatr 132:445–451CrossRefPubMed Weirich E, Rabin R, Maldonado Y, Benitz W, Modler S, Herzenberg L (1998) Neutrophil CD11b expression as a diagnostic marker for early-onset neonatal infection. J Pediatr 132:445–451CrossRefPubMed
30.
go back to reference Zen K, Cui L, Zhang C, Liu Y (2007) Critical role of Mac-1 sialyl Lewis x moieties in regulating neutrophil degranulation and transmigration. J Mol Biol 374:54–63CrossRefPubMed Zen K, Cui L, Zhang C, Liu Y (2007) Critical role of Mac-1 sialyl Lewis x moieties in regulating neutrophil degranulation and transmigration. J Mol Biol 374:54–63CrossRefPubMed
Metadata
Title
CD15s is a potential biomarker of serious bacterial infection in infants admitted to hospital
Authors
Josko Markic
Ana Jeroncic
Denis Polancec
Nada Bosnjak
Anita Markotic
Julije Mestrovic
Vedrana Cikes Culic
Publication date
01-10-2013
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Pediatrics / Issue 10/2013
Print ISSN: 0340-6199
Electronic ISSN: 1432-1076
DOI
https://doi.org/10.1007/s00431-013-2047-y

Other articles of this Issue 10/2013

European Journal of Pediatrics 10/2013 Go to the issue