Mannose-binding lectin and mannose-binding lectin–associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults - 13/08/11
Reprint requests: Carlos Rodriguez-Gallego, PhD, Servicio de Inmunología, Hospital Universitario de Gran Canaria Dr Negrín, Barranco de la Ballena s/n, 35010 Las Palmas de Gran Canaria, Spain.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.
Le texte complet de cet article est disponible en PDF.Key words : Community-acquired pneumonia, sepsis, mannose-binding lectin, mannose-binding lectin–associated serine protease 2, primary immunodeficiency
Abbreviations used : ARDS, ARF, CAP, ICU, LP, MASP-2, MBL, MODS, OR, PGN, SS, SSh
Plan
| Supported by the “Fondo de Investigaciones Sanitarias” (Ministerio de Sanidad) with the funding of the European Regional Development Fund–European Social Fund (FEDER-FSE; FIS 02/1620 and 04/1190), “Sociedad Española de Neumología y Cirugía Torácica” (SEPAR 2002), RedRespira-ISCiii-RTIC-03/11 (Instituto de Salud Carlos III, Ministerio de Sanidad), and FUNCIS (Gobierno de Canarias, INREDCAN 5/06). M. Isabel García-Laorden was supported by a grant from the Fundacion Canaria Dr Manuel Morales and by the Fundacion Canaria de Investigacion y Salud (FUNCIS; Proyecto Biorregion 2006). Ayoze García-Saavedra was supported by a grant from the Cabildo de Gran Canaria (Grant Tomas de Zarate 15725). |
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| Disclosure of potential conflict of interest: The authors have declared that they have no conflict of interest. |
Vol 122 - N° 2
P. 368 - août 2008 Retour au numéro
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