TY - JOUR
T1 - Mannose-binding lectin genotype is associated with respiratory disease in young children
T2 - A multicenter cohort study
AU - Ruffles, Tom
AU - Basu, Kaninika
AU - Inglis, Sarah K.
AU - Bremner, Stephen
AU - Rabe, Heike
AU - Memon, Anjum
AU - Seddon, Paul
AU - Tavendale, Roger
AU - Palmer, Colin N. A.
AU - Mukhopadhyay, Somnath
AU - Fidler, Katy
N1 - Funding Information:
The study was funded by the medical charity Sparks (grant number G0010) and Rockinghorse Children’s Charity. We received additional funding from the Brighton and Sussex Medical School. The study was sponsored by Brighton and Sussex University Hospitals NHS Trust who provided grant funding for operational costs of the project.
Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2022/11
Y1 - 2022/11
N2 - Background: Mannose-binding lectin (MBL) is an important component of the innate immune system. Polymorphisms in the MBL2 gene and promoter region are directly associated with MBL-deficiency. We sought to determine the association between MBL genotype on the frequency of common childhood respiratory infections, respiratory symptoms, and atopic outcomes in early childhood. Methods: MBL2 gene variants were analyzed in newborns recruited to the GO-CHILD multicenter prospective cohort study. Follow-up for respiratory infection and atopy diagnoses and symptoms, healthcare utilization, and medication prescription were conducted by postal questionnaires at 12 and 24 months. Results: Genotyping and follow-up were completed in 1004 children. Genotypes associated with MBL-deficiency were associated with an increased risk of bronchiolitis (relative risk [RR] 1.95, 95% confidence interval [CI] 1.33–2.85) and pneumonia (RR 2.46, 95% CI 1.16–5.22). MBL-deficient genotypes were associated with an increased risk of wheeze with shortness of breath episodes (RR 1.22, 95% CI 1.04–1.43), emergency department attendance (RR 1.90 95% CI 1.13–3.19), and hospital admission (RR 2.01, 95% CI 1.04–3.89) for wheeze. MBL-deficient genotypes were associated with a reduced risk of developing atopic dermatitis (RR 0.72, 95% CI 0.53–0.98). Conclusion: The positive association between MBL-deficient genotypes and bronchiolitis and pneumonia, as well as a severe wheeze phenotype in some young children, supports the hypothesis that MBL is an important component of innate immunity in the vulnerable period before the maturation of the adaptive immune system. Identification of disease-modifying genotypes may help target preventative strategies in high-risk infants.
AB - Background: Mannose-binding lectin (MBL) is an important component of the innate immune system. Polymorphisms in the MBL2 gene and promoter region are directly associated with MBL-deficiency. We sought to determine the association between MBL genotype on the frequency of common childhood respiratory infections, respiratory symptoms, and atopic outcomes in early childhood. Methods: MBL2 gene variants were analyzed in newborns recruited to the GO-CHILD multicenter prospective cohort study. Follow-up for respiratory infection and atopy diagnoses and symptoms, healthcare utilization, and medication prescription were conducted by postal questionnaires at 12 and 24 months. Results: Genotyping and follow-up were completed in 1004 children. Genotypes associated with MBL-deficiency were associated with an increased risk of bronchiolitis (relative risk [RR] 1.95, 95% confidence interval [CI] 1.33–2.85) and pneumonia (RR 2.46, 95% CI 1.16–5.22). MBL-deficient genotypes were associated with an increased risk of wheeze with shortness of breath episodes (RR 1.22, 95% CI 1.04–1.43), emergency department attendance (RR 1.90 95% CI 1.13–3.19), and hospital admission (RR 2.01, 95% CI 1.04–3.89) for wheeze. MBL-deficient genotypes were associated with a reduced risk of developing atopic dermatitis (RR 0.72, 95% CI 0.53–0.98). Conclusion: The positive association between MBL-deficient genotypes and bronchiolitis and pneumonia, as well as a severe wheeze phenotype in some young children, supports the hypothesis that MBL is an important component of innate immunity in the vulnerable period before the maturation of the adaptive immune system. Identification of disease-modifying genotypes may help target preventative strategies in high-risk infants.
KW - atopic
KW - bronchiolitis
KW - mannose-binding lectin
KW - pneumonia and dermatitis
KW - respiratory tract infections
UR - http://www.scopus.com/inward/record.url?scp=85136870938&partnerID=8YFLogxK
U2 - 10.1002/ppul.26109
DO - 10.1002/ppul.26109
M3 - Article
C2 - 35949104
SN - 8755-6863
VL - 57
SP - 2824
EP - 2833
JO - Pediatric Pulmonology
JF - Pediatric Pulmonology
IS - 11
ER -