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
- 111 Downloads
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.
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.
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).
This study shows that baseline MBL > 1870 ng/ml is associated with higher mortality in ICU patients with severe A(H1N1)pdm09 infection.
KeywordsMannose-binding lectin Pandemic influenza A 2009 (H1N1) ICU Mortality
Adjusted hazard ratio
Acute respiratory distress syndrome
Area under the curve
Bronchoalveolar lavage fluid
Chronic obstructive pulmonary disease
Extracorporeal membrane oxygenation
Intensive care unit
Negative likelihood ratio
Negative predictive value
Positive likelihood ratio
Positive predictive value
Receiver operating characteristic
Real-time polymerase chain reaction
- SAPS II
Simplified acute physiology score
Sequential organ failure assessment
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.
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.
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.
This study was approved by the Institutional Review Board for Human Subjects.
Patients or relatives provided their informed consent.
- 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
- 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.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