Mannose-binding lectin and mannose-binding lectin–associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults

• Published in: Journal of allergy and clinical immunology Vol. 122; no. 2; pp. 368 - 374.e2
• Main Authors: Garcia-Laorden, M. Isabel, BSc, Sole-Violan, Jordi, PhD, de Castro, Felipe Rodriguez, PhD, Aspa, Javier, PhD, Briones, M. Luisa, PhD, Garcia-Saavedra, Ayoze, BSc, Rajas, Olga, PhD, Blanquer, Jose, PhD, Caballero-Hidalgo, Araceli, BEc, Marcos-Ramos, J. Alberto, MD, Hernandez-Lopez, Javier, BSc, Rodriguez-Gallego, Carlos, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.08.2008; Elsevier; Elsevier Limited
• Subjects: Adult; Aged; Alleles; Allergy and Immunology; Biological and medical sciences; Case-Control Studies; Chronic obstructive pulmonary disease; Community-Acquired Infections - genetics; Community-acquired pneumonia; Drug therapy; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Kaplan-Meier Estimate; Male; mannose-binding lectin; Mannose-Binding Lectin - blood; Mannose-Binding Lectin - deficiency; Mannose-Binding Lectin - genetics; Mannose-Binding Lectin - physiology; mannose-binding lectin–associated serine protease 2; Mannose-Binding Protein-Associated Serine Proteases - analysis; Mannose-Binding Protein-Associated Serine Proteases - deficiency; Mannose-Binding Protein-Associated Serine Proteases - genetics; Medical sciences; Middle Aged; Mortality; Pneumonia; Pneumonia, Bacterial - genetics; Pneumonia, Bacterial - metabolism; Pneumonia, Bacterial - physiopathology; Pneumonia, Pneumococcal - genetics; Pneumonia, Pneumococcal - metabolism; Pneumonia, Pneumococcal - physiopathology; Polymorphism, Genetic; primary immunodeficiency; Prospective Studies; Respiratory distress syndrome; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; sepsis; Severity of Illness Index; Acute respiratory distress syndrome; LP; Severe sepsis; SSh; Intensive care unit; MODS; Mannose-binding lectin serine protease 2; MBL; primary immunodeficiency; ARDS; SS; OR; Lectin pathway; Multiple organ dysfunction syndrome; Septic shock; Community-acquired pneumonia; Peptidoglycan; CAP; ARF; MASP-2; PGN; Acute respiratory failure; Odds ratio; ICU; sepsis; mannose-binding lectin; mannose-binding lectin–associated serine protease 2; Pneumonia; Prognosis; Mannose binding lectin; mannose-binding lectin-associated serine protease 2; mannose- binding lectin; Sepsis syndrome; Immunology; Primary; Adult; Evolution; Human; Lung disease; Immunopathology; Serine endopeptidases; Enzyme; Respiratory disease; Severity; Immune deficiency; Bacteremia; Infection; Peptidases; Sensitivity; Community acquired infection; Bacteriosis; Hydrolases
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2008.05.037

Background Community-acquired pneumonia (CAP) is the leading cause of death from infection in developed countries. Mannose-binding lectin (MBL) and MBL-associated serine protease 2 (MASP-2) deficiencies are common primary immunodeficiencies the clinical penetrance of which remains controversial. MBL is a serum lectin that mediates phagocytosis and activates the lectin pathway of complement involving MASP-2. Objective We sought to evaluate the significance of MBL deficiency ( O/O genotypes) and insufficiency ( O/O plus XA/O genotypes), as well as MASP-2 deficiency ( D105G mutation), in the susceptibility to and severity and outcome of CAP in adults. Methods MBL and MASP-2 serum levels, as well as lectin pathway activity with regard to MBL2 and MASP2 genotypes, were measured in healthy control subjects. For susceptibility, 848 patients with CAP, 1447 healthy control subjects, and a control group of 519 patients without relevant infectious diseases were studied in a case-control study. Severity and outcome were evaluated in a prospective study of the 848 patients. Results We found similar frequencies of MBL2 and MASP2 alleles and genotypes among patients and control subjects. However, in a multivariate analysis MBL insufficiency was associated with the development of the most severe forms of sepsis ( P = .007), acute respiratory failure ( P = .009), multiorgan dysfunction syndrome ( P = .036), intensive care unit admission ( P = .020), and death ( P = .003). Conclusion Our large study suggests that MBL plays a redundant role in human defenses against primary infection, at least in adults with CAP, and provides, for the first time, evidence that MBL insufficiency predisposes to higher severity and fatal outcome in patients with CAP, irrespective of the causal microorganisms.