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Lung

, Volume 196, Issue 1, pp 65–72 | Cite as

Prospective Observational Study on the Association Between Serum Mannose-Binding Lectin Levels and Severe Outcome in Critically Ill Patients with Pandemic Influenza Type A (H1N1) Infection

  • Elie Zogheib
  • Remy Nyga
  • Marjorie Cornu
  • Boualem Sendid
  • Julien Monconduit
  • Vincent Jounieaux
  • Julien Maizel
  • Christine Segard
  • Taïeb Chouaki
  • Hervé Dupont
ACUTE LUNG INJURY
  • 111 Downloads

Abstract

Background

Mannose-binding lectin (MBL) plays an important role in the innate immune response. In addition to activating the complement, MBL can induce cytokine production and contribute to a deleterious inflammatory response with severe A(H1N1)pdm09 virus infection. Our aim was to determine if serum MBL levels correlate with the risk of mortality in intensive care units (ICU) patients with A(H1N1)pdm09 infection.

Methods

Prospective observational study was performed in ICU patients with acute respiratory distress syndrome due to influenza A(H1N1)pdm09 virus. Demographic characteristics and severity indices were recorded at ICU admission. MBL was assayed from blood drawn at influenza diagnosis within 24–48 h following the ICU admission. Outcomes were compared according to MBL levels. Results are expressed as median and interquartile range.

Results

Serum MBL levels were studied in 27 patients (age: 56 [IQR 29] years) with severe A(H1N1)pdm09 infection and in 70 healthy controls. Median admission SAPSII and SOFA scores were 49 [IQR 26] and 12 [IQR 5], respectively. Mortality rate after a 30-day was 37%. MBL was significantly higher in non-survivors (3741 [IQR 2336] ng/ml) vs survivors (215 [IQR 1307] ng/ml), p = 0.006, as well as control group (1814 [IQR 2250] ng/ml), p = 0.01. In contrast, MBL levels in survivors group were significantly lower than the controls group (215 [IQR 1307] ng/ml vs. 1814 [IQR 2250] ng/ml, p = 0.005). MBL cut-off > 1870 ng/ml had a sensitivity of 80% and a specificity of 88.2% for mortality [AUC = 0.82 (95% CI 0.63–0.94)]. Kaplan–Meier analysis demonstrated a strong association between MBL levels and mortality (log-rank 7.8, p = 0.005). MBL > 1870 ng/ml was independently associated with mortality (HR = 8.7, 95% CI 1.2–29.1, p = 0.007).

Conclusions

This study shows that baseline MBL > 1870 ng/ml is associated with higher mortality in ICU patients with severe A(H1N1)pdm09 infection.

Keywords

Mannose-binding lectin Pandemic influenza A 2009 (H1N1) ICU Mortality 

Abbreviations

aHR

Adjusted hazard ratio

ARDS

Acute respiratory distress syndrome

AUC

Area under the curve

BALF

Bronchoalveolar lavage fluid

COPD

Chronic obstructive pulmonary disease

ECMO

Extracorporeal membrane oxygenation

ICU

Intensive care unit

IQR

Interquartile range

MBL

Mannose-binding lectin

NLR

Negative likelihood ratio

NPV

Negative predictive value

OD

Optical density

PLR

Positive likelihood ratio

PPV

Positive predictive value

ROC

Receiver operating characteristic

RT-PCR

Real-time polymerase chain reaction

SAPS II

Simplified acute physiology score

SOFA

Sequential organ failure assessment

Notes

Acknowledgements

The authors would like to thank all of the patients for their participation in this study. The cooperation of the medical and paramedical staff of intensive care units of the University Hospital, Amiens, France, is gratefully acknowledged.

Authors’ contributions

EZ, RN, TC, and HD contributed to the conception and design of the study. EZ, RN, and TC performed the acquisition of the data. HD performed the statistical analysis. EZ, RN, TC, JM, VJ, JM, CS, SB, and HD contributed to the analysis and interpretation of data, wrote and approved the final manuscript. EZ, RN, TC, JM, VJ, JM, CS, SB, and HD gave agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Funding

This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

Compliance with ethical standards

Conflict of interest

All the authors declare that they have no conflict of interest.

Ethical approval

This study was approved by the Institutional Review Board for Human Subjects.

Informed consent

Patients or relatives provided their informed consent.

References

  1. 1.
    Ferguson ND, Fan E, Camporota L et al (2012) The Berlin definition of ARDS: an expanded rationale, justification, and supplementary material. Intensive Care Med 38:1573–1582.  https://doi.org/10.1007/s00134-012-2682-1 CrossRefPubMedGoogle Scholar
  2. 2.
    Olson DR, Simonsen L, Edelson PJ, Morse SS (2005) Epidemiological evidence of an early wave of the 1918 influenza pandemic in New York City. Proc Natl Acad Sci USA 102:11059–11063.  https://doi.org/10.1073/pnas.0408290102 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Andreasen V, Viboud C, Simonsen L (2008) Epidemiologic characterization of the 1918 influenza pandemic summer wave in Copenhagen: implications for pandemic control strategies. J Infect Dis 197:270–278.  https://doi.org/10.1086/524065 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Mulrennan S, Tempone SS, Ling ITW et al (2010) Pandemic influenza (H1N1) 2009 pneumonia: CURB-65 score for predicting severity and nasopharyngeal sampling for diagnosis are unreliable. PLoS ONE 5:e12849.  https://doi.org/10.1371/journal.pone.0012849 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lee N, Wong CK, Chan PKS et al (2011) Cytokine response patterns in severe pandemic 2009 H1N1 and seasonal influenza among hospitalized adults. PLoS ONE 6:e26050.  https://doi.org/10.1371/journal.pone.0026050 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Shi X, Zhou W, Huang H et al (2013) Inhibition of the inflammatory cytokine tumor necrosis factor-alpha with etanercept provides protection against lethal H1N1 influenza infection in mice. Crit Care 17:R301.  https://doi.org/10.1186/cc13171 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Rondina MT, Tatsumi K, Bastarache JA, Mackman N (2016) Microvesicle tissue factor activity and interleukin-8 levels are associated with mortality in patients with influenza A/H1N1 infection. Crit Care Med 44:e574–e578.  https://doi.org/10.1097/CCM.0000000000001584 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Kawasaki T (1999) Structure and biology of mannan-binding protein, MBP, an important component of innate immunity. Biochim Biophys Acta 1473:186–195CrossRefPubMedGoogle Scholar
  9. 9.
    Fujita T, Matsushita M, Endo Y (2004) The lectin-complement pathway—its role in innate immunity and evolution. Immunol Rev 198:185–202CrossRefPubMedGoogle Scholar
  10. 10.
    Ip WKE, Takahashi K, Ezekowitz RA, Stuart LM (2009) Mannose-binding lectin and innate immunity. Immunol Rev 230:9–21.  https://doi.org/10.1111/j.1600-065X.2009.00789.x CrossRefPubMedGoogle Scholar
  11. 11.
    Ling MT, Tu W, Han Y et al (2012) Mannose-binding lectin contributes to deleterious inflammatory response in pandemic H1N1 and avian H9N2 infection. J Infect Dis 205:44–53.  https://doi.org/10.1093/infdis/jir691 CrossRefPubMedGoogle Scholar
  12. 12.
    Perez-Castellano M, Peñaranda M, Payeras A et al (2006) Mannose-binding lectin does not act as an acute-phase reactant in adults with community-acquired pneumococcal pneumonia. Clin Exp Immunol 145:228–234.  https://doi.org/10.1111/j.1365-2249.2006.03140.x CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Dean MM, Minchinton RM, Heatley S, Eisen DP (2005) Mannose binding lectin acute phase activity in patients with severe infection. J Clin Immunol 25:346–352.  https://doi.org/10.1007/s10875-005-4702-1 CrossRefPubMedGoogle Scholar
  14. 14.
    Eisen DP, Dean MM, Boermeester MA et al (2008) Low serum mannose-binding lectin level increases the risk of death due to pneumococcal infection. Clin Infect Dis 47:510–516.  https://doi.org/10.1086/590006 CrossRefPubMedGoogle Scholar
  15. 15.
    Hartshorn KL, Sastry K, White MR et al (1993) Human mannose-binding protein functions as an opsonin for influenza A viruses. J Clin Invest 91:1414–1420.  https://doi.org/10.1172/JCI116345 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kase T, Suzuki Y, Kawai T et al (1999) Human mannan-binding lectin inhibits the infection of influenza A virus without complement. Immunology 97:385–392CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Anders EM, Hartley CA, Reading PC, Ezekowitz RA (1994) Complement-dependent neutralization of influenza virus by a serum mannose-binding lectin. J Gen Virol 75(Pt 3):615–622.  https://doi.org/10.1099/0022-1317-75-3-615 CrossRefPubMedGoogle Scholar
  18. 18.
    Guo J, Cao Y, Qin K et al (2015) Limited effect of recombinant human mannose-binding lectin on the infection of novel influenza A (H7N9) virus in vitro. Biochem Biophys Res Commun 458:77–81.  https://doi.org/10.1016/j.bbrc.2015.01.070 CrossRefPubMedGoogle Scholar
  19. 19.
    Berger SP, Roos A, Mallat MJK et al (2007) Low pretransplantation mannose-binding lectin levels predict superior patient and graft survival after simultaneous pancreas-kidney transplantation. J Am Soc Nephrol 18:2416–2422.  https://doi.org/10.1681/ASN.2007030262 CrossRefPubMedGoogle Scholar
  20. 20.
    Homann C, Garred P, Hasselqvist P et al (1995) Mannan-binding protein and complement dependent opsonization in alcoholic cirrhosis. Liver 15:39–44CrossRefPubMedGoogle Scholar
  21. 21.
    Jack DL, Jarvis GA, Booth CL et al (2001) Mannose-binding lectin accelerates complement activation and increases serum killing of Neisseria meningitidis serogroup C. J Infect Dis 184:836–845.  https://doi.org/10.1086/323204 CrossRefPubMedGoogle Scholar
  22. 22.
    Nadesalingam J, Dodds AW, Reid KBM, Palaniyar N (2005) Mannose-binding lectin recognizes peptidoglycan via the N-acetyl glucosamine moiety, and inhibits ligand-induced proinflammatory effect and promotes chemokine production by macrophages. J Immunol 175:1785–1794CrossRefPubMedGoogle Scholar
  23. 23.
    Wang M, Wang F, Yang J et al (2013) Mannan-binding lectin inhibits Candida albicans-induced cellular responses in PMA-activated THP-1 cells through Toll-like receptor 2 and Toll-like receptor 4. PLoS ONE 8:e83517.  https://doi.org/10.1371/journal.pone.0083517 CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Garcia-Laorden MI, Sole-Violan J, Rodriguez de Castro F, et al (2008) Mannose-binding lectin and mannose-binding lectin-associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults. J Allergy Clin Immunol 122:368–374, 374–382.  https://doi.org/10.1016/j.jaci.2008.05.037
  25. 25.
    García-Laorden MI, Rodríguez de Castro F, Solé-Violán J et al (2013) The role of mannose-binding lectin in pneumococcal infection. Eur Respir J 41:131–139.  https://doi.org/10.1183/09031936.00174111 CrossRefPubMedGoogle Scholar
  26. 26.
    Wong M, Öhrmalm L, Broliden K et al (2012) Mannose-binding lectin 2 polymorphisms do not influence frequency or type of infection in adults with chemotherapy induced neutropaenia. PLoS ONE 7:e30819.  https://doi.org/10.1371/journal.pone.0030819 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Dahl M, Tybjaerg-Hansen A, Schnohr P, Nordestgaard BG (2004) A population-based study of morbidity and mortality in mannose-binding lectin deficiency. J Exp Med 199:1391–1399.  https://doi.org/10.1084/jem.20040111 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Petersen SV, Thiel S, Jensenius JC (2001) The mannan-binding lectin pathway of complement activation: biology and disease association. Mol Immunol 38:133–149CrossRefPubMedGoogle Scholar
  29. 29.
    Delgado C, Krötzsch E, Jiménez-Alvarez LA et al (2015) Serum surfactant protein D (SP-D) is a prognostic marker of poor outcome in patients with A/H1N1 virus infection. Lung 193:25–30.  https://doi.org/10.1007/s00408-014-9669-3 CrossRefPubMedGoogle Scholar
  30. 30.
    Sin DD, Leung R, Gan WQ, Man SP (2007) Circulating surfactant protein D as a potential lung-specific biomarker of health outcomes in COPD: a pilot study. BMC Pulm Med 7:13.  https://doi.org/10.1186/1471-2466-7-13 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  • Elie Zogheib
    • 1
    • 2
  • Remy Nyga
    • 3
  • Marjorie Cornu
    • 4
    • 5
  • Boualem Sendid
    • 4
    • 5
  • Julien Monconduit
    • 6
  • Vincent Jounieaux
    • 6
  • Julien Maizel
    • 2
    • 7
  • Christine Segard
    • 8
  • Taïeb Chouaki
    • 3
  • Hervé Dupont
    • 1
    • 2
  1. 1.Cardiothoracic and Vascular Intensive Care UnitAmiens University HospitalAmiensFrance
  2. 2.INSERM U1088Jules Verne University of PicardyAmiensFrance
  3. 3.Medical Parasitology and Mycology DepartmentAmiens University HospitalAmiensFrance
  4. 4.Medical Parasitology and Mycology DepartmentCHULilleFrance
  5. 5.INSERM U995, Team Fungal Associated Invasive & Inflammatory Diseases, Lille Inflammation Research International CenterUniversité de LilleLilleFrance
  6. 6.Respiratory Intensive Care UnitAmiens University HospitalAmiensFrance
  7. 7.Medical Intensive Care UnitAmiens University HospitalAmiensFrance
  8. 8.Medical Virology DepartmentAmiens University HospitalAmiensFrance

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