BACKGROUND: Siblings have been shown to reduce the risk of later asthma and allergy, but the mechanism driving this association is unknown. The objective was to study whether siblings affect the airway immune response in healthy neonates. We hypothesized that siblings exert immune modulatory effects on neonates mirrored in the airway mucosa. METHODS: We measured 20 immune-mediators related to the Type 1, Type 2, Type 17 or regulatory immune pathways in the airway mucosa of 571 one-month-old asymptomatic neonates from the Copenhagen Prospective Studies on Asthma in Childhood2010 birth-cohort (COPSAC2010). The association between airway mediator levels and presence of siblings was investigated using conventional statistics and principle component analyses (PCA). RESULTS: Neonates with siblings had an up-regulated level of airway immune-mediators, with predominance of Type 1- and Type 17-related mediators. This was supported by the PCA showing a highly significant difference between children with vs. without siblings: p<10-10, which persisted after adjustment for potential confounders including pathogenic airway bacteria and viruses: p<0.0001. The immune priming effect was inversely associated with time since last childbirth: p=0.0015. CONCLUSIONS: Siblings mediate a Type 1/Type 17-related immune-stimulatory effect in the airways of asymptomatic neonates, also after adjustment for pathogenic bacteria and viruses, indicating that siblings exert a transferable early immune modulatory effect. These findings may represent an in-utero immune priming effect of the fetal immune system caused by previous pregnancies as the effect was attenuated with time since last childbirth or presence of unidentified microbes, but further studies are needed to confirm our findings.
- Mucosal lining fluid