Looman Kirsten I M, van Mierlo Minke M F, van Zelm Menno C, Hu Chen, Duijts Liesbeth, de Jongste Johan C, Nijsten Tamar, Pardo Luba M, Kiefte-de Jong Jessica C, Moll Henriëtte A, Pasmans Suzanne G M A
The Generation R Study Group, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Department of General Pediatrics, Erasmus MC, University Medical Center Rotterdam-Sophia Children's Hospital, Rotterdam, The Netherlands.
Pediatr Allergy Immunol. 2021 Aug;32(6):1360-1368. doi: 10.1111/pai.13502. Epub 2021 Mar 29.
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.
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.
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.
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.
丝聚合蛋白基因（FLG）突变会影响表皮屏障功能，并增加患特应性皮炎（AD）的风险。我们推测FLG突变会影响普通儿科人群的免疫细胞组成。因此，我们调查了有无FLG突变的学龄儿童在T细胞和B细胞亚群上是否存在差异。
本研究纳入了一项基于人群的前瞻性队列研究——“Generation R研究”，研究对象为523名10岁的欧洲遗传血统儿童。对欧洲人群中最常见的FLG突变（R501X、S1085CfsX36、R2447X和S3247X）进行基因分型。此外还对外周血样本进行了11色流式细胞术检测，以确定辅助性T细胞（Th）、调节性T细胞（Treg）以及CD27和CD27记忆B细胞。通过家长问卷评估，在358例非AD病例和102例AD病例中进行了亚群分析。
在总人口的8.4%以及AD病例的15.7%中观察到FLG突变。在普通人群和非AD人群中，与FLG野生型儿童相比，任何FLG突变的儿童Th22细胞数量都更高。有无FLG突变的儿童在Thl、Th2、Th17、Treg或记忆B细胞数量上没有差异。此外，在AD儿童中，FLG突变携带者与T细胞和B细胞亚群的差异无关。
普通人群中有FLG突变的学龄儿童Th22细胞数量更高，这反映了对皮肤屏障功能障碍的免疫反应。在这个普通儿科人群中，FLG突变在其他方面并未影响适应性免疫的组成。
