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International Journal of Pediatrics
Volume 2013 (2013), Article ID 763191, 6 pages
http://dx.doi.org/10.1155/2013/763191
Review Article

Flow Cytometry in the Detection of Neonatal Sepsis

Department of Neonatology, Children’s Hospital, University Hospital of RWTH Aachen, Pauwelsstraße 30, 52074 Aachen, Germany

Received 12 October 2012; Revised 10 January 2013; Accepted 11 January 2013

Academic Editor: Khalid N. Haque

Copyright © 2013 Volker N. Umlauf et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. B. J. Stoll, N. I. Hansen, P. J. Sánchez, et al., “Early onset neonatal sepsis: the burden of group B Streptococcal and E. coli disease continues,” Pediatrics, vol. 127, no. 5, pp. 817–826, 2011.
  2. A. Jaiswal, S. Murki, P. Gaddam, and A. Reddy, “Early neonatal morbidities in late preterm infants,” Indian Pediatrics, vol. 48, no. 8, pp. 607–611, 2011.
  3. B. J. Stoll, N. I. Hansen, R. D. Higgins et al., “Very low birth weight preterm infants with early onset neonatal sepsis: the predominance of Gram-negative infections continues in the National Institute of Child Health and Human Development Neonatal Research Network, 2002-2003,” Pediatric Infectious Disease Journal, vol. 24, no. 7, pp. 635–639, 2005. View at Publisher · View at Google Scholar · View at Scopus
  4. L. Maródi, “Innate cellular immune responses in newborns,” Clinical Immunology, vol. 118, no. 2-3, pp. 137–144, 2006.
  5. C. Gille, T. W. Orlikowsky, B. Spring, et al., “Monocytes derived from humanized neonatal NOD/SCID/IL2Rγ(null) mice are phenotypically immature and exhibit functional impairments,” Human Immunology, vol. 73, no. 4, pp. 346–354, 2012.
  6. E. Hotoura, V. Giapros, A. Kostoula, P. Spirou, and S. Andronikou, “Tracking changes of lymphocyte subsets and pre-inflammatory mediators in full-term neonates with suspected or documented infection,” Scandinavian Journal of Immunology, vol. 73, no. 3, pp. 250–255, 2011. View at Publisher · View at Google Scholar · View at Scopus
  7. C. Gille, A. Leiber, I. Mundle et al., “Phagocytosis and postphagocytic reaction of cord blood and adult blood monocyte after infection with green fluorescent protein-labeled Escherichia coli and group B Streptococci,” Cytometry B, vol. 76, no. 4, pp. 271–284, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. U. Hallwirth, G. Pomberger, A. Pollak, E. Roth, and A. Spittler, “Monocyte switch in neonates: high phagocytic capacity and low HLA-DR expression in VLBWI are inverted during gestational aging,” Pediatric Allergy and Immunology, vol. 15, no. 6, pp. 513–516, 2004. View at Publisher · View at Google Scholar · View at Scopus
  9. T. Strunk, P. Temming, U. Gembruch, I. Reiss, P. Bucsky, and C. Schultz, “Differential maturation of the innate immune response in human fetuses,” Pediatric Research, vol. 56, no. 2, pp. 219–226, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. C. Schultz, C. Rott, P. Temming, P. Schlenke, J. C. Möller, and P. Bucsky, “Enhanced interleukin-6 and interleukin-8 synthesis in term and preterm infants,” Pediatric Research, vol. 51, no. 3, pp. 317–322, 2002. View at Scopus
  11. A. Leviton, T. M. O’Shea, F. J. Bednarek, et al., “Systemic responses of preterm newborns with presumed or documented bacteraemia,” Acta Paediatrica, vol. 101, no. 4, pp. 355–359, 2012.
  12. W. A. Luce, T. M. Hoffman, and J. A. Bauer, “Bench-to-bedside review: developmental influences on the mechanisms, treatment and outcomes of cardiovascular dysfunction in neonatal versus adult sepsis,” Critical Care, vol. 11, no. 5, article 228, 2007. View at Publisher · View at Google Scholar · View at Scopus
  13. M. Gantert, J. V. Been, A. W. D. Gavilanes, et al., “Chorioamnionitis: a multiorgan disease of the fetus?” Journal of Perinatology, vol. 30, supplement, pp. S21–S30, 2010.
  14. D. Payen, V. Faivre, A. C. Lukaszewicz, F. Villa, and P. Goldberg, “Expression of monocyte human leukocyte antigen-DR in relation with sepsis severity and plasma mediators,” Minerva Anestesiologica, vol. 75, no. 9, pp. 484–493, 2009. View at Scopus
  15. A. Takala, I. Nupponen, M. L. Kylänpää-Bäck, and H. Repo, “Markers of inflammation in sepsis,” Annals of Medicine, vol. 34, no. 7-8, pp. 614–623, 2002.
  16. C. Gille, B. Spring, L. J. Tewes et al., “Diminished response to interleukin-10 and reduced antibody-dependent cellular cytotoxicity of cord blood monocyte-derived macrophages,” Pediatric Research, vol. 60, no. 2, pp. 152–157, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. Y. K. Choo, H. S. Cho, I. B. Seo, and H. S. Lee, “Comparison of the accuracy of neutrophil CD64 and C-reactive protein as a single test for the early detection of neonatal sepsis,” Korean Journal of Pediatrics, vol. 55, no. 1, p. 11, 2012.
  18. P. C. Ng, K. Li, R. P. O. Wong, K. M. Chui, E. Wong, and T. F. Fok, “Neutrophil CD64 expression: a sensitive diagnostic marker for late-onset nosocomial infection in very low birthweight infants,” Pediatric Research, vol. 51, no. 3, pp. 296–303, 2002. View at Scopus
  19. C. Gille, F. Steffen, K. Lauber et al., “Clearance of apoptotic neutrophils is diminished in cord blood monocytes and does not lead to reduced IL-8 production,” Pediatric Research, vol. 66, no. 5, pp. 507–512, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. O. Dammann, D. Ferriero, and P. Gressens, “Neonatal encephalopathy or hypoxic-ischemic encephalopathy? Appropriate terminology matters,” Pediatric Research, vol. 70, no. 1, pp. 1–2, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. P. C. Ng, G. Li, K. M. Chui et al., “Neutrophil CD64 is a sensitive diagnostic marker for early-onset neonatal infection,” Pediatric Research, vol. 56, no. 5, pp. 796–803, 2004. View at Publisher · View at Google Scholar · View at Scopus
  22. I. Streimish, M. Bizzarro, V. Northrup, et al., “Neutrophil CD64 as a diagnostic marker in neonatal sepsis,” The Pediatric Infectious Disease Journal, vol. 31, no. 7, pp. 777–781, 2012.
  23. I. Nupponen, S. Andersson, A. L. Järvenpää, H. Kautiainen, and H. Repo, “Neutrophil CD11b expression and circulating interleukin-8 as diagnostic markers for early-onset neonatal sepsis,” Pediatrics, vol. 108, no. 1, p. E12, 2001. View at Scopus
  24. V. Bhandari, C. Wang, C. Rinder, and H. Rinder, “Hematologic profile of sepsis in neonates: neutrophil CD64 as a diagnostic marker,” Pediatrics, vol. 121, no. 1, pp. 129–134, 2008. View at Publisher · View at Google Scholar · View at Scopus
  25. M. Adib, V. Ostadi, F. Navaei et al., “Evaluation of CD11b expression on peripheral blood neutrophils for early detection of neonatal sepsis,” Iranian Journal of Allergy, Asthma and Immunology, vol. 6, no. 2, pp. 93–96, 2007. View at Scopus
  26. Y. B. Cui, L. Z. Du, Y. Z. Chen, Y. B. Yu, F. M. Wang, and Q. Q. Mao, “Expression of neutrophil adhesion molecule CD11b as an early diagnostic marker for neonatal sepsis,” Chinese Journal of Pediatrics, vol. 41, no. 5, pp. 348–351, 2003. View at Scopus
  27. W. E. Benitz, “Adjunct laboratory tests in the diagnosis of early-onset neonatal sepsis,” Clinics in Perinatology, vol. 37, no. 2, pp. 421–438, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. E. Siewert, W. Müller-Esterl, R. Starr, P. C. Heinrich, and F. Schaper, “Different protein turnover of interleukin-6-type cytokine signalling components,” European Journal of Biochemistry, vol. 265, no. 1, pp. 251–257, 1999. View at Publisher · View at Google Scholar · View at Scopus
  29. C. Buck, J. Bundschu, H. Gallati, P. Bartmann, and F. Pohlandt, “Interleukin-6: a sensitive parameter for the early diagnosis of neonatal bacterial infection,” Pediatrics, vol. 93, no. 1, pp. 54–58, 1994. View at Scopus
  30. F. Genel, F. Atlihan, E. Ozsu, and E. Ozbek, “Monocyte HLA-DR expression as predictor of poor outcome in neonates with late onset neonatal sepsis,” Journal of Infection, vol. 60, no. 3, pp. 224–228, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. D. Andaluz-Ojeda, V. Iglesias, F. Bobillo, et al., “Early natural killer cell counts in blood predict mortality in severe sepsis,” Critical Care, vol. 15, no. 5, p. R243, 2011.
  32. F. Venet, A. Lepape, and G. Monneret, “Clinical review: flow cytometry perspectives in the ICU—from diagnosis of infection to monitoring of injury-induced immune dysfunctions,” Critical Care, vol. 15, no. 5, p. 231, 2011.
  33. P. C. Ng, “Clinical trials for evaluating diagnostic markers of infection in neonates,” Biology of the Neonate, vol. 87, no. 2, pp. 111–112, 2005. View at Publisher · View at Google Scholar · View at Scopus
  34. F. Nimmerjahn and J. V. Ravetch, “Fcγ receptors: old friends and new family members,” Immunity, vol. 24, no. 1, pp. 19–28, 2006. View at Publisher · View at Google Scholar · View at Scopus
  35. W. van der Meer, P. Pickkers Peter, C. S. Scott, J. G. van der Hoeven, and J. K. Gunnewiek, “Hematological indices, inflammatory markers and neutrophil CD64 expression: comparative trends during experimental human endotoxemia,” Journal of Endotoxin Research, vol. 13, no. 2, pp. 94–100, 2007. View at Publisher · View at Google Scholar · View at Scopus
  36. D. Dilli, Ş. S. Oguz, U. Dilmen, M. Y. Köker, and M. KiZiLgün, “Predictive values of neutrophil CD64 expression compared with interleukin-6 and C-reactive protein in early diagnosis of neonatal sepsis,” Journal of Clinical Laboratory Analysis, vol. 24, no. 6, pp. 363–370, 2010. View at Publisher · View at Google Scholar · View at Scopus
  37. S. Soni, N. Wadhwa, R. Kumar, M. M. Faridi, et al., “Evaluation of CD64 expression on neutrophils as an early indicator of neonatal sepsis,” The Pediatric Infectious Disease Journal, vol. 32, no. 1, pp. e33–e37, 2012.
  38. J. J. M. L. Hoffmann, “Neutrophil CD64: a diagnostic marker for infection and sepsis,” Clinical Chemistry and Laboratory Medicine, vol. 47, no. 8, pp. 903–916, 2009. View at Publisher · View at Google Scholar · View at Scopus
  39. F. Genel, F. Atlihan, N. Gulez, et al., “Evaluation of adhesion molecules CD64, CD11b and CD62L in neutrophils and monocytes of peripheral blood for early diagnosis of neonatal infection,” World Journal of Pediatrics, vol. 8, no. 1, pp. 72–75, 2012.
  40. E. Hotoura, V. Giapros, A. Kostoula, et al., “Pre-inflammatory mediators and lymphocyte subpopulations in preterm neonates with sepsis,” Inflammation, vol. 35, no. 3, pp. 1094–1101, 2012.
  41. A. D. Aygun, A. N. Citak Kurt, A. Godekmerdan et al., “Neonates with culture proven sepsis have lower amounts and percentage of CD45RA+ T cells,” Inflammation, vol. 31, no. 4, pp. 222–226, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. F. Kanakoudi-Tsakalidou, F. Debonera, V. Drossou-Agakidou et al., “Flow cytometric measurement of HLA-DR expression on circulating monocytes in healthy and sick neonates using monocyte negative selection,” Clinical and Experimental Immunology, vol. 123, no. 3, pp. 402–407, 2001. View at Publisher · View at Google Scholar · View at Scopus
  43. Y. Fan and J. L. Yu, “Umbilical blood biomarkers for predicting early-onset neonatal sepsis,” World Journal of Pediatrics WJP, vol. 8, no. 2, pp. 101–108, 2012.
  44. L. L. Raynor, J. J. Saucerman, M. O. Akinola, et al., “Cytokine screening identifies NICU patients with Gram-negative bacteremia,” Pediatric Research, vol. 71, no. 3, pp. 261–266, 2012.
  45. R. L. Schelonka, A. Maheshwari, W. A. Carlo et al., “T cell cytokines and the risk of blood stream infection in extremely low birth weight infants,” Cytokine, vol. 53, no. 2, pp. 249–255, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. J. D. M. Edgar, V. Gabriel, J. R. Gallimore, S. A. McMillan, and J. Grant, “A prospective study of the sensitivity, specificity and diagnostic performance of soluble intercellular adhesion molecule 1, highly sensitive C-reactive protein, soluble E-selectin and serum amyloid A in the diagnosis of neonatal infection,” BMC Pediatrics, vol. 10, article 22, 2010. View at Publisher · View at Google Scholar · View at Scopus
  47. M. E. S. Zaki and H. El Sayed, “Evaluation of microbiologic and hematologic parameters and E-selectin as early predictors for outcome of neonatal sepsis,” Archives of Pathology and Laboratory Medicine, vol. 133, no. 8, pp. 1291–1296, 2009. View at Scopus
  48. J. Figueras-Aloy, L. Gómez-López, J. M. Rodríguez-Miguélez, et al., “Serum soluble ICAM-1, VCAM-1, L-selectin, and P-selectin levels as markers of infection and their relation to clinical severity in neonatal sepsis,” American Journal of Perinatology, vol. 24, no. 6, pp. 331–338, 2007.
  49. R. Austgulen, K. J. Arntzen, P. E. Hæreid, S. Aag, and H. Døllner, “Infections in neonates delivered at term are associated with increased serum levels of ICAM-1 and E-selectin,” Acta Paediatrica, International Journal of Paediatrics, vol. 86, no. 3, pp. 274–280, 1997. View at Scopus
  50. S. Gibot, M. C. Bene, R. Noel, F. Massin, et al., “Combination biomarkers to diagnose sepsis in the critically Ill patient,” American Journal of Respiratory and Critical Care Medicine, vol. 186, no. 1, pp. 65–71, 2012.
  51. D. A. Solovjov, E. Pluskota, and E. F. Plow, “Distinct roles for the α and β subunits in the functions of integrin αMβ2,” Journal of Biological Chemistry, vol. 280, no. 2, pp. 1336–1345, 2005. View at Publisher · View at Google Scholar · View at Scopus
  52. M. A. Arnaout, R. F. Todd, N. Dana, et al., “Inhibition of phagocytosis of complement C3- or immunoglobulin G-coated particles and of C3bi binding by monoclonal antibodies to a monocyte-granulocyte membrane glycoprotein (Mo1),” Journal of Clinical Investigation, vol. 72, no. 1, pp. 171–179, 1983. View at Scopus
  53. R. Turunen, O. Vaarala, I. Nupponen et al., “Activation of T cells in preterm infants with respiratory distress syndrome,” Neonatology, vol. 96, no. 4, pp. 248–258, 2009. View at Publisher · View at Google Scholar · View at Scopus
  54. P. C. Ng, G. Li, K. M. Chui, et al., “Quantitative measurement of monocyte HLA-DR expression in the identification of early-onset neonatal infection,” Biology of the Neonate, vol. 89, no. 2, pp. 75–81, 2006. View at Publisher · View at Google Scholar · View at Scopus
  55. G. Hodge, S. Hodge, P. Han, and R. Haslam, “Multiple leucocyte activation markers to detect neonatal infection,” Clinical and Experimental Immunology, vol. 135, no. 1, pp. 125–129, 2004. View at Publisher · View at Google Scholar · View at Scopus
  56. W. D. Döcke, C. Höflich, K. A. Davis, et al., “Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study,” Clinical Chemistry, vol. 51, no. 12, pp. 2341–2347, 2005.
  57. R. S. Hotchkiss, C. M. Coopersmith, and I. E. Karl, “Prevention of lymphocyte apoptosis—a potential treatment of sepsis?” Clinical Infectious Diseases, vol. 41, no. 7, pp. S465–S469, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. C. A. Liu, C. L. Wang, F. S. Wang et al., “Higher spontaneous and TNFα-induced apoptosis of neonatal blood granulocytes,” Pediatric Research, vol. 58, no. 1, pp. 132–137, 2005. View at Publisher · View at Google Scholar · View at Scopus
  59. D. H. Watts, M. A. Krohn, S. L. Hillier, and D. A. Eschenbach, “Bacterial vaginosis as a risk factor for post-cesarean endometritis,” Obstetrics and Gynecology, vol. 75, no. 1, pp. 52–58, 1990. View at Scopus
  60. D. Viemann, G. Dubbel, S. Schleifenbaum, E. Harms, C. Sorg, and J. Roth, “Expression of toll-like receptors in neonatal sepsis,” Pediatric Research, vol. 58, no. 4, pp. 654–659, 2005. View at Publisher · View at Google Scholar · View at Scopus
  61. L. A. Herzenberg, R. G. Sweet, and L. A. Herzenberg, “Fluorescence-activated cell sorting,” Scientific American, vol. 234, no. 3, pp. 108–117, 1976. View at Scopus