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


CONCLUSIONS
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.
Garcia-Laorden
M Isabel
MI
Department of Immunology, Hospital Universitario de Gran Canaria Dr Negrín, Las Palmas de Gran Canaria, Spain.
Sole-Violan
Jordi
J
Rodriguez de Castro
Felipe
F
Aspa
Javier
J
Briones
M Luisa
ML
Garcia-Saavedra
Ayoze
A
Rajas
Olga
O
Blanquer
Jose
J
Caballero-Hidalgo
Araceli
A
Marcos-Ramos
J Alberto
JA
Hernandez-Lopez
Javier
J
Rodriguez-Gallego
Carlos
C
D000328:Adult; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D017714:Community-Acquired Infections / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D037601:Mannose-Binding Lectin / Q000097:blood / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D050606:Mannose-Binding Protein-Associated Serine Proteases / Q000032:analysis / Q000172:deficiency / Q000235:genetics*; D008875:Middle Aged; D018410:Pneumonia, Bacterial / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D011018:Pneumonia, Pneumococcal / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012720:Severity of Illness Index
C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; C105296:MASP2 protein, human; D050606:Mannose-Binding Protein-Associated Serine Proteases