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Title: Mannose-binding lectin and mannose-binding lectin-associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults
Authors: Garcia-Laorden, M. Isabel
Sole-Violan, Jordi
de Castro, Felipe Rodriguez 
Aspa, Javier
Briones, M. Luisa
Garcia-Saavedra, Ayoze
Rajas, Olga
Blanquer, Jose
Caballero-Hidalgo, Araceli
Marcos-Ramos, J. Alberto
Hernandez-Lopez, Javier
Rodriguez-Gallego, Carlos 
UNESCO Clasification: 32 Ciencias médicas
320508 Enfermedades pulmonares
Keywords: Community-acquired pneumonia
Mannose-binding lectin
Mannose-binding lectin–associated serine protease 2
Primary immunodeficiency
Issue Date: 2008
Journal: Journal of Allergy and Clinical Immunology 
Abstract: 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.
ISSN: 0091-6749
DOI: 10.1016/j.jaci.2008.05.037
Source: Journal of Allergy and Clinical Immunology [ISSN 0091-6749], v. 122, p. 368-374
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