Mannose-binding lectin genotype in relation to childhood respiratory infection and atopy outcomes: a multi-centre cohort study

Abstract

<b>Background:</b> Mannose binding lectin (MBL) plays a central role in the innate immune system. MBL2 gene and promoter region polymorphisms are associated with MBL-deficiency. <b>Aims:</b> To examine the association between MBL genotype and common childhood respiratory infections, respiratory symptoms, and atopic outcomes in early childhood. <b>Methods:</b> We analysed MBL2 variants in newborns recruited to the GO-CHILD multi-centre cohort study. Children were grouped as MBL-deficient (YO/YO, XA/YO), intermediate (XA/XA, YA/YO) or sufficient (XA/YA, YA/YA). Questionnaires were completed at 12 and 24-months to assess respiratory infection and atopy diagnoses and symptoms, medications, and healthcare utilisation. <b>Results:</b> Follow-up was completed in 1004 children. MBL-deficient genotypes were associated with an increased risk of bronchiolitis (relative risk (RR) 1.95, 95%CI 1.33-2.85; p=0.001), recurrent bronchiolitis (RR 4.45, 95%CI 2.17-9.14; p&lt;0.001) and pneumonia (RR 2.48, 95%CI 1.18-5.21; p=0.016). MBL-deficient genotypes were associated with wheeze related emergency department attendance (RR 1.86 95%CI 1.10-3.14; p=0.020) and hospital admission (RR 1.99, 95%CI 1.02-3.83; p=0.041), as well as an increased risk of wheeze with shortness of breath episodes (RR 1.61, 95%CI 1.17-2.23; p=0.016). There was a reduced risk of atopic dermatitis (RR 0.71, 95%CI 0.52-0.96; p=0.029) with MBL-deficient genotypes. <b>Conclusion:</b> Our findings support the hypothesis that MBL is an important component of innate immunity in the vulnerable period preceding the maturation of the adaptive immune system. Identification of children with MBL-deficient genotypes may help target preventative interventions.