Department of Dermatology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei krt, Debrecen, 4032, Hungary; Department of Dermatological Allergology, Medical and Health Science Center, University of Debrecen, 98 Nagyerdei krt, Debrecen, 4032, Hungary.
Br J Dermatol. 2014 Mar;170(3):617-24. doi: 10.1111/bjd.12743.
Filaggrin (FLG) deficiency is a well-known predisposing factor for the development of atopic dermatitis (AD). Decreased FLG expression can be the result of haploinsufficiency or severe inflammation, which can cause acquired FLG alterations. FLG mutations are related to several clinical and laboratory parameters of AD; however, some recent data seem to contradict these associations.
Our aim was to determine which clinical and biochemical parameters are connected to FLG haploinsufficiency and which ones are also associated with acquired FLG alterations due to severe skin symptoms in patients with AD.
We introduced a novel classification of patients with AD, based on FLG mutations and SCORAD (SCORing Atopic Dermatitis). Based on these parameters, we created three groups of patients with AD: mild-to-moderate wild-type (A), severe wild-type (B) and severe mutant (C). In all groups, we assessed laboratory and clinical parameters and performed immunohistochemical analyses.
Groups B and C contained patients with equally severe symptoms based on the SCORAD. The two severe groups did not differ significantly with respect to barrier-specific parameters, whereas group A had significantly better results for the barrier function measurements. However, significant differences were detected between groups B and C with respect to the allergic sensitization-specific parameters.
These findings suggest that skin barrier function correlates with the severity of skin inflammation and can be equally impaired in patients with FLG mutant- and wild-type AD with severe symptoms. Nevertheless, our results also suggest that patients with FLG mutant-type AD may have a higher risk of allergic sensitization compared with patients with the wild-type.
丝聚蛋白（FLG）缺陷是特应性皮炎（AD）发展的一个已知的易感因素。FLG 表达减少可能是由于单倍体不足或严重炎症导致的获得性 FLG 改变。FLG 突变与 AD 的几个临床和实验室参数有关；然而，一些最近的数据似乎与这些关联相矛盾。
我们的目的是确定哪些临床和生化参数与 FLG 单倍体不足有关，哪些与 AD 患者因严重皮肤症状导致的获得性 FLG 改变有关。
我们根据 FLG 突变和 SCORAD（特应性皮炎评分）引入了一种新的 AD 患者分类。基于这些参数，我们创建了三组 AD 患者：轻度至中度野生型（A）、严重野生型（B）和严重突变型（C）。在所有组中，我们评估了实验室和临床参数并进行了免疫组织化学分析。
根据 SCORAD，B 组和 C 组均包含症状严重的患者。这两个严重组在屏障特异性参数方面没有显著差异，而 A 组的屏障功能测量结果明显更好。然而，B 组和 C 组在过敏致敏特异性参数方面存在显著差异。
这些发现表明，皮肤屏障功能与皮肤炎症的严重程度相关，在具有严重症状的 FLG 突变型和野生型 AD 患者中可能同样受损。然而，我们的结果还表明，与野生型患者相比，FLG 突变型 AD 患者可能有更高的过敏致敏风险。
