Diminished HLA-DR expression on monocyte and dendritic cell subsets indicating impairment of cellular immunity in pre-term neonates: a prospective observational analysis

Joerg C. Schefold; Linn Porz; Barbara Uebe; Holger Poehlmann; Stephan von Haehling; Andreas Jung; Nadine Unterwalder; Christian Meisel

doi:10.1515/jpm-2014-0226

Article

Diminished HLA-DR expression on monocyte and dendritic cell subsets indicating impairment of cellular immunity in pre-term neonates: a prospective observational analysis

Joerg C. Schefold , Linn Porz , Barbara Uebe , Holger Poehlmann , Stephan von Haehling , Andreas Jung , Nadine Unterwalder and Christian Meisel

Published/Copyright: October 25, 2014

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From the journal Journal of Perinatal Medicine Volume 43 Issue 5

Abstract

Aims: The risk of neonates for severe infection/sepsis is reciprocally proportional to gestational age and birth weight. As monocytes and dendritic cells (DC) are recognised key antigen-presenting immune cells, we aimed to elucidate whether neonatal age is associated with reduced expression of human-leukocyte antigen-DR (HLA-DR) antigens on subsets of monocytes and DCs.

Methods: Forty-three consecutive neonates (20 male, mean gestational age 236.0±26.8 days; mean 1-min Apgar score 7.5±2.0) were included in a monocentric prospective observational analysis. Patients were grouped according to gestational age (n=15 full-term, n=28 pre-term defined as <33 weeks). Ten healthy adult volunteers were assessed also. Flow-cytometric assessment of HLA-DR expression was performed in subsets of peripheral blood myeloid and plasmacytoid DCs (MDC and PDC) and monocytes (CD14^brightCD16^negative/CD14^positiveCD16^positive/CD14^dimCD16^positive). Clinical and routine laboratory data were followed up.

Results: At birth, leukocyte counts were increased in full-term neonates. Monocyte counts were significantly increased in neonates when compared with adults (all P<0.05). A significant numerical increase of CD14^brightCD16^negative and CD14^positiveCD16^positive monocytes was noted in pre-term and full-term neonates (all P<0.05), while HLA-DR expression in these subsets was significantly diminished (most pronounced in pre-term infants, P<0.0001). MDC and PDC HLA-DR expression was reduced also (all P<0.05). Clinical indices (e.g., pH, days on antibiotics/mechanical ventilation, fever/sepsis) were not found to correlate with immunological indices.

Conclusions: We observed a markedly diminished HLA-DR expression on monocyte and DC subsets in pre-term and full-term neonates, which may contribute to impaired antimicrobial defence mechanisms in the early days of life.

Keywords: Dendritic cells; HLA-DR; immunoparalysis; inflammation; monocytes; organ failure; sepsis; septic shock; severe infection

Corresponding author: Joerg C. Schefold, MD, Department of Intensive Care Medicine, University Hospital of Bern, Inselspital CH 3010 Bern, Switzerland, Phone: +41-31-63 25397, E-mail: joerg.schefold@insel.ch; and Department of Nephrology and Intensive Care Medicine, Charité Universitätsmedizin Berlin, Campus Vichow Clinic, Augustenburger Platz 1, Berlin, Germany

aDeceased.

Acknowledgments

The authors thank all ICU and laboratory staff for their dedicated help and support.

Competing interests: The authors declare that they have no competing interests to declare.

Authors’ contributions: JCS and CM designed the trial, investigated all data, and wrote the manuscript. LP, HP, and AJ were responsible for patient recruitment and patient management, recorded all data, and assisted in the interpretation of all data. SVH participated together with JCS and CM in the interpretation and statistical analysis of all data and revised the manuscript for important intellectual content.

References

[1] Adkins B, Leclerc C, Marshall-Clarke S. Neonatal adaptive immunity comes of age. Nat Rev Immunol. 2004;4:553–64.Search in Google Scholar

[2] Christensen RD, Anstall HB, Rothstein G. Review: deficiencies in the neutrophil system of newborn infants, and the use of leukocyte transfusions in the treatment of neonatal sepsis. J Clin Apher. 1982;1:33–41.Search in Google Scholar

[3] Gentile LF, Nacionales DC, Lopez MC, Vanzant E, Cuenca A, Cuenca AG, et al. Protective immunity and defects in the neonatal and elderly immune response to sepsis. J Immunol. 2014 (epub ahead of print).Search in Google Scholar

[4] Kovarik J, Siegrist CA. Immunity in early life. Immunol Today. 1998;19:150–2.Search in Google Scholar

[5] Velilla PA, Rugeles MT, Chougnet CA. Defective antigen-presenting cell function in human neonates. Clin Immunol. 2006;121:251–9.Search in Google Scholar

[6] Andrews P, Azoulay E, Antonelli M, Brochard L, Brun-Buisson C, Dobb G, et al. Year in review in intensive care medicine, 2004. III. Outcome, ICU organisation, scoring, quality of life, ethics, psychological problems and communication in the ICU, immunity and hemodynamics during sepsis, pediatric and neonatal critical care, experimental studies. Intensive Care Med. 2005;31:356–72.Search in Google Scholar

[7] Hotchkiss RS, Monneret G, Payen D. Sepsis-induced immunosuppression: from cellular dysfunctions to immunotherapy. Nat Rev Immunol. 2013;13:862–74.Search in Google Scholar

[8] Schefold JC, Hasper D, Reinke P, Monneret G, Volk HD. Consider delayed immunosuppression into the concept of sepsis. Crit Care Med. 2008;36:3118.Search in Google Scholar

[9] Schefold JC, Hasper D, Volk HD, Reinke P. Sepsis: time has come to focus on the later stages. Med Hypotheses. 2008;71:203–8.Search in Google Scholar

[10] Meisel C, Schwab JM, Prass K, Meisel A, Dirnagl U. Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci. 2005;6:775–86.Search in Google Scholar

[11] Meisel C, Schefold JC, Pschowski R, Baumann T, Hetzger K, Gregor J, et al. Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial. Am J Respir Crit Care Med. 2009;180:640–8.Search in Google Scholar

[12] Schefold JC, von Haehling S, Corsepius M, Pohle C, Kruschke P, Zuckermann H, et al. A novel selective extracorporeal intervention in sepsis: immunoadsorption of endotoxin, interleukin 6, and complement-activating product 5a. Shock. 2007;28:418–25.Search in Google Scholar

[13] Gladstone IM, Ehrenkranz RA, Edberg SC, Baltimore RS. A ten-year review of neonatal sepsis and comparison with the previous fifty-year experience. Pediatr Infect Dis J. 1990;9:819–25.Search in Google Scholar

[14] Hallwirth U, Pomberger G, Pollak A, Roth E, Spittler A. Monocyte switch in neonates: high phagocytic capacity and low HLA-DR expression in VLBWI are inverted during gestational aging. Pediatr Allergy Immunol. 2004;15:513–6.Search in Google Scholar

[15] Huang X, Venet F, Chung CS, Lomas-Neira J, Ayala A. Changes in dendritic cell function in the immune response to sepsis. Cell- & tissue-based therapy. Expert Opin Biol Ther. 2007;7:929–38.Search in Google Scholar

[16] Poehlmann H, Schefold JC, Zuckermann-Becker H, Volk HD, Meisel C. Phenotype changes and impaired function of dendritic cell subsets in patients with sepsis: a prospective observational analysis. Crit Care. 2009;13:R119.Search in Google Scholar

[17] Docke WD, Hoflich C, Davis KA, Rottgers K, Meisel C, Kiefer P, et al. Monitoring temporary immunodepression by flow cytometric measurement of monocytic HLA-DR expression: a multicenter standardized study. Clin Chem. 2005;51:2341–7.Search in Google Scholar

The authors stated that there are no conflicts of interest regarding the publication of this article.

Received: 2014-7-15

Accepted: 2014-9-26

Published Online: 2014-10-25

Published in Print: 2015-9-1

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Articles in the same Issue

https://doi.org/10.1515/jpm-2014-0226

Keywords for this article

Dendritic cells; HLA-DR; immunoparalysis; inflammation; monocytes; organ failure; sepsis; septic shock; severe infection