University Eye Hospital, University Medical Centre Freiburg, Freiburg im Breisgau, Germany.
Int Arch Allergy Immunol. 2014;163(1):20-4. doi: 10.1159/000355965. Epub 2013 Nov 16.
Filaggrin is expressed in the epidermis and is essential for the maintenance of the epidermal barrier. Null mutations within the filaggrin gene (FLG) lead to a disturbed epidermal barrier and are associated with a significantly increased risk of atopic dermatitis (AD). The association of AD with ocular surface disorders prompted us to speculate that common FLG mutations may be particularly prevalent in AD patients with ocular comorbidities.
Corneal buttons and biopsies from AD patients with ocular involvement (n = 11) and from non-atopic patients (n = 9) with a histological diagnosis of keratitis were included in the study. DNA samples obtained from paraffin-embedded corneal specimens were genotyped for the two most common FLG mutations (R501X and 2282del4). Filaggrin protein expression was analysed by immunohistochemistry.
Normal skin and corneal specimens (n = 6) were positive for filaggrin, which could be detected in the stratum corneum of the skin and in the basal epithelial layer of the cornea. Interestingly, all AD corneal specimens as well as the specimens from keratitis patients without AD were negative for filaggrin expression. Genotyping of the FLG mutations R501X and 2282del4 revealed wild-type alleles in all analysed samples.
The lack of filaggrin expression observed in the analysed corneal specimens from AD patients is not due to the two most common FLG mutations (R501X, 2282del4) but is most likely secondary to inflammation, as all keratitis specimens of non-AD patients showed lack of filaggrin expression as well.
丝聚合蛋白在表皮中表达，对于维持表皮屏障至关重要。丝聚合蛋白基因（FLG）内的无义突变会导致表皮屏障紊乱，并与特应性皮炎（AD）的风险显著增加相关。AD 与眼表疾病的关联促使我们推测，常见的 FLG 突变在伴有眼部并发症的 AD 患者中可能特别普遍。
纳入了 11 例眼部受累的 AD 患者的角膜纽扣和活检组织，以及 9 例非特应性、组织学诊断为角膜炎的患者的活检组织。从石蜡包埋的角膜标本中获得的 DNA 样本用于检测两种最常见的 FLG 突变（R501X 和 2282del4）。通过免疫组织化学分析丝聚合蛋白蛋白的表达。
正常皮肤和角膜标本（n=6）均为丝聚合蛋白阳性，可在皮肤角质层和角膜基底上皮层检测到。有趣的是，所有 AD 角膜标本以及无 AD 的角膜炎患者的标本均未检测到丝聚合蛋白表达。FLG 突变 R501X 和 2282del4 的基因分型显示所有分析样本均为野生型等位基因。
在分析的 AD 患者的角膜标本中观察到的丝聚合蛋白表达缺失不是由于两种最常见的 FLG 突变（R501X、2282del4）引起的，而是很可能继发于炎症，因为所有非 AD 角膜炎患者的标本也显示缺乏丝聚合蛋白表达。
