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Mannose-binding lectin and mannose-binding lectin-associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults.
J Allergy Clin Immunol. 2008 Aug; 122(2):368-74, 374.e1-2.JA

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.

Authors+Show Affiliations

Department of Immunology, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18582923

Citation

Garcia-Laorden, M Isabel, et al. "Mannose-binding Lectin and Mannose-binding Lectin-associated Serine Protease 2 in Susceptibility, Severity, and Outcome of Pneumonia in Adults." The Journal of Allergy and Clinical Immunology, vol. 122, no. 2, 2008, pp. 368-74, 374.e1-2.
Garcia-Laorden MI, Sole-Violan J, Rodriguez de Castro F, et al. Mannose-binding lectin and mannose-binding lectin-associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults. J Allergy Clin Immunol. 2008;122(2):368-74, 374.e1-2.
Garcia-Laorden, M. I., Sole-Violan, J., Rodriguez de Castro, F., Aspa, J., Briones, M. L., Garcia-Saavedra, A., Rajas, O., Blanquer, J., Caballero-Hidalgo, A., Marcos-Ramos, J. A., Hernandez-Lopez, J., & Rodriguez-Gallego, C. (2008). Mannose-binding lectin and mannose-binding lectin-associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults. The Journal of Allergy and Clinical Immunology, 122(2), 368-74, e1-2. https://doi.org/10.1016/j.jaci.2008.05.037
Garcia-Laorden MI, et al. Mannose-binding Lectin and Mannose-binding Lectin-associated Serine Protease 2 in Susceptibility, Severity, and Outcome of Pneumonia in Adults. J Allergy Clin Immunol. 2008;122(2):368-74, 374.e1-2. PubMed PMID: 18582923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mannose-binding lectin and mannose-binding lectin-associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults. AU - Garcia-Laorden,M Isabel, AU - Sole-Violan,Jordi, AU - Rodriguez de Castro,Felipe, AU - Aspa,Javier, AU - Briones,M Luisa, AU - Garcia-Saavedra,Ayoze, AU - Rajas,Olga, AU - Blanquer,Jose, AU - Caballero-Hidalgo,Araceli, AU - Marcos-Ramos,J Alberto, AU - Hernandez-Lopez,Javier, AU - Rodriguez-Gallego,Carlos, Y1 - 2008/06/25/ PY - 2008/02/11/received PY - 2008/05/16/revised PY - 2008/05/27/accepted PY - 2008/6/28/pubmed PY - 2008/8/30/medline PY - 2008/6/28/entrez SP - 368-74, 374.e1-2 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 122 IS - 2 N2 - 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/18582923/Mannose_binding_lectin_and_mannose_binding_lectin_associated_serine_protease_2_in_susceptibility_severity_and_outcome_of_pneumonia_in_adults_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(08)01005-1 DB - PRIME DP - Unbound Medicine ER -