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Background  Mutations in the filaggrin gene ( FLG ) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that  FLG  mutations affect immune cell composition in a general pediatric population. Therefore, we investigated whether school‐aged children with and without  FLG  mutations have differences in T‐ and B‐cell subsets.    Methods  This study was embedded in a population‐based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common  FLG  mutations in the European population (R501X, S1085CfsX36, R2447X, and S3247X) were genotyped. Additionally, 11‐color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg), and CD27 +  and CD27 ‐  memory B cells. Subset analysis was performed in 358 non‐AD and 102 AD cases, assessed by parental questionnaires.    Results   FLG  mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any  FLG  mutation had higher Th22 cell numbers compared to  FLG  wild‐type children in the general and non‐AD population. Children with and without  FLG  mutations had no difference in Th1, Th2, Th17, Treg, or memory B‐cell numbers. Furthermore, in children with AD,  FLG  mutation carriership was not associated with differences in T‐ and B‐cell subsets.    Conclusions  School‐aged children of a general population with  FLG  mutations have higher Th22 cell numbers, which reflects the immunological response to the skin barrier dysfunction.  FLG  mutations did not otherwise affect the composition of the adaptive immunity in this general pediatric population.

Increased Th22 cell numbers in a general pediatric population with filaggrin haploinsufficiency: The Generation R Study