• M Isabel Garcia-Laorden, Jordi Sole-Violan, Felipe Rodriguez de Castro, Javier Aspa, M Luisa Briones, Ayoze Garcia-Saavedra, Olga Rajas, Jose Blanquer, Araceli Caballero-Hidalgo, J Alberto Marcos-Ramos, Javier Hernandez-Lopez, and Carlos Rodriguez-Gallego.
• Department of Immunology, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain.
• J. Allergy Clin. Immunol. 2008 Aug 1; 122 (2): 368-74, 374.e1-2.

BackgroundCommunity-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.ObjectiveWe 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.MethodsMBL 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.ResultsWe 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).ConclusionOur 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.

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