Department of Dermatology, Shimane University Faculty of Medicine, Izumo, Japan.
Center for Supercentenarian Medical Research, Keio University School of Medicine, Tokyo, Japan.
J Dermatol. 2021 Nov;48(11):1688-1699. doi: 10.1111/1346-8138.16087. Epub 2021 Jul 29.
Loss-of-function mutations of filaggrin (FLG) gene (FLG) are the strongest known genetic risk factor for atopic dermatitis (AD). It is still debatable how FLG gene mutations and the resulting abnormal amount of FLG protein contribute to skin barrier function and symptoms of AD. In this study, we examined the effects of loss-of-function mutations of FLG gene on the severity of skin lesions and skin barrier function in 55 patients with AD by evaluating eight patients with AD with FLG gene mutations and 47 patients with AD without mutations. The results showed that the FLG gene mutation did not affect the duration of AD, severity of AD, degree of local inflammatory symptoms, skin water content and trans-epidermal water loss of the lesions. Next, in these eight mutation carriers and the 47 non-carriers, stratum corneum was collected from the three site of skin lesions using tape-stripping method, and the amounts of FLG protein and total amino acid contained in the stratum corneum was measured to investigate the effect of the FLG gene mutation on the amount of FLG gene product in the local lesion. FLG abnormalities had little effect on FLG protein and total amino acid content in the stratum corneum in the lesional skin. The amount of the FLG products, especially amino acids derived from FLG, in the stratum corneum of AD lesional skin is influenced by development of dermatitis. The results obtained from this study supports that the activation of Th2-dominant inflammatory cells, together with FLG abnormality, plays a role in suppressing the production of FLG in skin lesions.
丝聚蛋白（FLG）基因突变是特应性皮炎（AD）最强的已知遗传风险因素。FLG 基因突变和由此导致的异常量的 FLG 蛋白如何导致皮肤屏障功能和 AD 症状仍然存在争议。在这项研究中，我们通过评估 8 名携带 FLG 基因突变的 AD 患者和 47 名无突变的 AD 患者，研究了 FLG 基因突变对 55 名 AD 患者皮损严重程度和皮肤屏障功能的影响。结果表明，FLG 基因突变不影响 AD 的持续时间、AD 的严重程度、局部炎症症状的严重程度、皮损皮肤水分含量和经表皮水分流失。接下来，在这 8 名突变携带者和 47 名非携带者中，我们使用胶带剥离法从皮损的三个部位采集角质层，测量角质层中 FLG 蛋白和总氨基酸的含量，以研究 FLG 基因突变对局部病变中 FLG 基因产物量的影响。FLG 异常对皮损皮肤角质层中 FLG 蛋白和总氨基酸含量的影响很小。AD 皮损皮肤角质层中 FLG 产物的量，特别是来自 FLG 的氨基酸的量，受皮炎的发展影响。本研究的结果支持 Th2 优势炎症细胞的激活与 FLG 异常一起在抑制皮肤病变中 FLG 的产生中起作用。
