This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (194)  • Contact me when this article is cited  Related Content  • Related articles  • Similar articles in JAMA  Topic Collections  • Pulmonary Diseases  • Pulmonary Diseases, Other  • Genetics  • Genetic Disorders  • Alert me on articles by topic  Social Bookmarking   What's this?

Anders Koch, MD,PhD; Mads Melbye, MD,DMSc; Per Sørensen, MSc; Preben Homøe, MD,PhD; Hans Ole Madsen, PhD; Kåre Mølbak, MD,DMSc; Christoffer Holst Hansen; Lasse Høgh Andersen; Gitte Weinkauff Hahn; Peter Garred, MD,DMSc

JAMA. 2001;285:1316-1321.

Context  Hospital-based studies have found that increased susceptibility to certain infections is associated with low serum levels of mannose-binding lectin (MBL) due to MBL variant alleles. However, the contribution of MBL insufficiency to incidence of common childhood infections at a population level is unknown.

Objective  To investigate the effect of MBL insufficiency on risk for acute respiratory tract infection (ARI) in unselected children younger than 2 years.

Design and Setting  Population-based, prospective, cohort study conducted in Sisimiut, Greenland.

Participants  Two hundred fifty-two children younger than 2 years who were followed up weekly between August 1996 and August 1998 for morbidity surveillance.

Main Outcome Measure  Risk of ARI, based on medical history and clinical examination, compared by MBL genotype, determined from blood samples based on presence of structural and promoter alleles.

Results  A 2.08-fold (95% confidence interval [CI], 1.41-3.06) increased relative risk (RR) of ARI was found in MBL-insufficient children (n = 13) compared with MBL-sufficient children (n = 239; P<.001). The risk association was largely restricted to children aged 6 to 17 months (RR, 2.92; 95% CI, 1.78-4.79) while less effect (RR, 1.47; 95% CI, 0.45-4.82) and no effect (RR, 1.00; 95% CI, 0.42-2.37) was shown among children aged 0 to 5 months and 18 to 23 months, respectively.

Conclusion  These data suggest that genetic factors such as MBL insufficiency play an important role in host defense, particularly during the vulnerable period of childhood from age 6 through 17 months, when the adaptive immune system is immature.

Author Affiliations: Department of Epidemiology Research, Statens Serum Institut (Drs Koch, Melbye, Sørensen, and Mølbak and Messrs Hansen and Andersen, and Ms Hahn); Departments of Otolaryngology, Head and Neck Surgery (Dr Homøe) and Clinical Immunology, Rigshospitalet, National University Hospital (Drs Madsen and Garred), Copenhagen, Denmark.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati     What's this?

RELATED ARTICLES

Why Do Some Individuals Have More Infections Than Others?
Jerry A. Winkelstein and Barton Childs
JAMA. 2001;285(10):1348-1349.
EXTRACT | FULL TEXT  

March 14, 2001
JAMA. 2001;285(10):1373-1374.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Macrophage-Specific Expression of Mannose-Binding Lectin Controls Atherosclerosis in Low-Density Lipoprotein Receptor-Deficient Mice
Matthijsen et al.
Circulation 2009;119:2188-2195.
ABSTRACT | FULL TEXT  

Mannose-binding lectin is present in the infected airway: a possible pulmonary defence mechanism
Fidler et al.
Thorax 2009;64:150-155.
ABSTRACT | FULL TEXT  

Mannose-Binding Lectin Genotypes in Susceptibility to Community-Acquired Pneumonia
Endeman et al.
Chest 2008;134:1135-1140.
ABSTRACT | FULL TEXT  

Mannose-binding lectin enhances Toll-like receptors 2 and 6 signaling from the phagosome
Ip et al.
JEM 2008;205:169-181.
ABSTRACT | FULL TEXT  

Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients
Hellemann et al.
Hum Mol Genet 2007;16:3071-3080.
ABSTRACT | FULL TEXT  

Lung Cancer Survival and Functional Polymorphisms in MBL2, an Innate-Immunity Gene
Pine et al.
JNCI J Natl Cancer Inst 2007;99:1401-1409.
ABSTRACT | FULL TEXT  

Low Pretransplantation Mannose-Binding Lectin Levels Predict Superior Patient and Graft Survival after Simultaneous Pancreas-Kidney Transplantation
Berger et al.
J. Am. Soc. Nephrol. 2007;18:2416-2422.
ABSTRACT | FULL TEXT  

Association between Mannose-Binding Lectin Deficiency and Septic Shock following Acute Pyelonephritis Due to Escherichia coli
Smithson et al.
CVI 2007;14:256-261.
ABSTRACT | FULL TEXT  

Coexistence of (Partial) Immune Defects and Risk of Recurrent Respiratory Infections
Bossuyt et al.
Clin. Chem. 2007;53:124-130.
ABSTRACT | FULL TEXT  

Synergy between mannose-binding lectin gene polymorphisms and supplementation with vitamin A influences susceptibility to HIV infection in infants born to HIV-positive mothers.
Kuhn et al.
Am. J. Clin. Nutr. 2006;84:610-615.
ABSTRACT | FULL TEXT  

Evolutionary insights into the high worldwide prevalence of MBL2 deficiency alleles
Verdu et al.
Hum Mol Genet 2006;15:2650-2658.
ABSTRACT | FULL TEXT  

Association of CD14 Promoter Polymorphism with Otitis Media and Pneumococcal Vaccine Responses.
Wiertsema et al.
CVI 2006;13:892-897.
ABSTRACT | FULL TEXT  

Mannose-binding lectin and upper respiratory tract infections in children and adolescents: a review.
Ruskamp et al.
Arch Otolaryngol Head Neck Surg 2006;132:482-486.
ABSTRACT | FULL TEXT  

Immune Status and Eustachian Tube Function in Recurrence of Otitis Media With Effusion
Straetemans et al.
Arch Otolaryngol Head Neck Surg 2005;131:771-776.
ABSTRACT | FULL TEXT  

Chronic Burkholderia multivorans bronchial infection in a non-cystic fibrosis individual with mannose binding lectin deficiency
Whitehouse et al.
Thorax 2005;60:168-170.
ABSTRACT | FULL TEXT  

Deficiency of somatic hypermutation of the antibody light chain is associated with increased frequency of severe respiratory tract infection in common variable immunodeficiency
Andersen et al.
Blood 2005;105:511-517.
ABSTRACT | FULL TEXT  

Impaired pulmonary status in cystic fibrosis adults with two mutated MBL-2 alleles
Davies et al.
Eur Respir J 2004;24:798-804.
ABSTRACT | FULL TEXT  

Glucocorticoids Suppress Inflammation but Spare Innate Immune Responses in Airway Epithelium
Schleimer
Proc Am Thorac Soc 2004;1:222-230.
ABSTRACT | FULL TEXT  

Fetal growth, maternal prenatal smoking, and risk of invasive meningococcal disease: a nationwide case-control study
Sorensen et al.
Int J Epidemiol 2004;33:816-820.
ABSTRACT | FULL TEXT  

Mannose-Binding Lectin Variant Alleles and the Risk of Arterial Thrombosis in Systemic Lupus Erythematosus
Ohlenschlaeger et al.
NEJM 2004;351:260-267.
ABSTRACT | FULL TEXT  

Association between Familial Deficiency of Mannose-Binding Lectin and Mutations in the Corresponding Gene and Promoter Region
Salimans et al.
CVI 2004;11:806-807.
ABSTRACT | FULL TEXT  

Association Between Mannose-Binding Lectin and Vascular Complications in Type 1 Diabetes
Hansen et al.
Diabetes 2004;53:1570-1576.
ABSTRACT | FULL TEXT  

Human Mannose-binding Lectin in Immunity: Friend, Foe, or Both?
Casanova and Abel
JEM 2004;199:1295-1299.
ABSTRACT | FULL TEXT  

A Population-based Study of Morbidity and Mortality in Mannose-binding Lectin Deficiency
Dahl et al.
JEM 2004;199:1391-1399.
ABSTRACT | FULL TEXT  

Disease-associated Mutations in Human Mannose-binding Lectin Compromise Oligomerization and Activity of the Final Protein
Larsen et al.
J. Biol. Chem. 2004;279:21302-21311.
ABSTRACT | FULL TEXT  

The roles of insulin and hyperglycemia in sepsis pathogenesis
Andersen et al.
J. Leukoc. Biol. 2004;75:413-421.
ABSTRACT | FULL TEXT  

Prospective Analysis of Mannose-Binding Lectin Genotypes and Coronary Artery Disease in American Indians: The Strong Heart Study
Best et al.
Circulation 2004;109:471-475.
ABSTRACT | FULL TEXT  

Modern Complement Analysis
Kirschfink and Mollnes
CVI 2003;10:982-989.
FULL TEXT  

Elevated Levels of Mannan-Binding Lectin in Patients with Type 1 Diabetes
Hansen et al.
J. Clin. Endocrinol. Metab. 2003;88:4857-4861.
ABSTRACT | FULL TEXT  

Mannose-Binding Lectin Is a Disease Modifier in Clinical Malaria and May Function as Opsonin for Plasmodium falciparum- Infected Erythrocytes
Garred et al.
Infect. Immun. 2003;71:5245-5253.
ABSTRACT | FULL TEXT  

Risk Factors for Acute Respiratory Tract Infections in Young Greenlandic Children
Koch et al.
Am J Epidemiol 2003;158:374-384.
ABSTRACT | FULL TEXT  

Total C4B Deficiency Due to Gene Deletion and Gene Conversion in a Patient with Severe Infections
Jaatinen et al.
CVI 2003;10:195-201.
ABSTRACT | FULL TEXT  

Increased frequency of mannose-binding lectin insufficiency among children with acute lymphoblastic leukemia
Schmiegelow et al.
Blood 2002;100:3757-3760.
ABSTRACT | FULL TEXT  

Contributions of the N- and C-Terminal Domains of Surfactant Protein D to the Binding, Aggregation, and Phagocytic Uptake of Bacteria
Hartshorn et al.
Infect. Immun. 2002;70:6129-6139.
ABSTRACT | FULL TEXT  

Association of Chlamydia pneumoniae With Coronary Artery Disease and Its Progression Is Dependent on the Modifying Effect of Mannose-Binding Lectin
Rugonfalvi-Kiss et al.
Circulation 2002;106:1071-1076.
ABSTRACT | FULL TEXT  

Mannose-binding lectin gene polymorphisms are associated with major infection following allogeneic hemopoietic stem cell transplantation
Mullighan et al.
Blood 2002;99:3524-3529.
ABSTRACT | FULL TEXT  

Why Do Some Individuals Have More Infections Than Others?
Winkelstein and Childs
JAMA 2001;285:1348-1349.
FULL TEXT