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Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels
Published on: August 7, 2017
Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood
1Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark. ako@ssi.dk
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.
Insights
Mannose-binding lectin (MBL) insufficiency significantly increases the risk of acute respiratory tract infections (ARI) in young children. This heightened susceptibility is most pronounced between 6 and 17 months of age, a critical period of immune development.
Area of Science:
- Immunology
- Pediatrics
- Genetics
Background:
- Low serum mannose-binding lectin (MBL) levels, often due to MBL variant alleles, are linked to increased infection susceptibility in hospital-based studies.
- The population-level impact of MBL insufficiency on common childhood infections remains largely unknown.
Purpose of the Study:
- To determine the association between MBL insufficiency and the risk of acute respiratory tract infection (ARI) in children under two years of age.
- Investigate the role of genetic factors in host defense against common childhood infections.
Main Methods:
- A population-based, prospective cohort study was conducted in Sisimiut, Greenland.
- 252 children under two years were monitored weekly for morbidity over two years.
- MBL genotype was determined from blood samples, and ARI risk was assessed based on clinical evaluations and medical history.
Main Results:
- MBL-insufficient children exhibited a 2.08-fold increased relative risk (RR) of ARI compared to MBL-sufficient children (P<.001).
- The increased risk was most significant in children aged 6-17 months (RR, 2.92).
- A lesser effect was observed in infants aged 0-5 months (RR, 1.47), with no significant effect in those aged 18-23 months (RR, 1.00).
Conclusions:
- Genetic factors, specifically MBL insufficiency, play a crucial role in children's immune defense against infections.
- This vulnerability is particularly evident during the 6-17 month age range, coinciding with an immature adaptive immune system.
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