Jun Myungsoo, Wang Hye Young, Lee Solam, Choi Eunhee, Lee Hyeyoung, Choi Eung Ho
Department of Dermatology, Yonsei University Wonju College of Medicine, Wonju, Korea.
Optipharm, Inc., Wonju Eco Environmental Technology Center, Wonju, Korea.
Allergy Asthma Immunol Res. 2018 May;10(3):244-252. doi: 10.4168/aair.2018.10.3.244.
Variations in barrier- or immune response-related genes are closely related to the development of atopic dermatitis (AD). This study was designed to identify genetic variations and clinical features to predict 'recalcitrant AD.'
AD patients were classified as treatable and recalcitrant. Treatable AD patients showed satisfactory clinical improvement with basic and topical treatments. Recalcitrant AD patients used systemic immune-suppressants for over 4 weeks as they had not shown clinical improvement with basic and topical treatments. The frequency of gene variations in barrier- (FLG 3321delA, FLG K4022X, KLK7, SPINK 1156, SPINK 1188, SPINK 2475) and immune response- (DEFB1, KDR, IL-5RA, IL-9, and IL-12RB1a, b) related genes were compared between each AD group and the controls.
Of all, 249 treatable AD and 32 recalcitrant AD were identified. Heterozygous mutations (Hetero) in KLK7 was more frequent in recalcitrant AD patients than treatable AD, without statistical significance. Hetero in DEFB1 was more frequent in treatable AD patients. However, no other significant genetic differences between treatable and recalcitrant AD was observed. Instead, higher initial Eczema Area Severity Index (EASI) score, serum immunoglobulin E (IgE) level, allergen specific IgE for house dust mites, and family history of atopic diseases were associated with recalcitrant AD with statistical significance.
According to our study, no genetic variation to predict recalcitrant AD was identified, suggesting that clinical manifestation, rather than genetic variations of AD patients is more likely to be an important factor in predicting the prognosis of AD. Further large-scale studies on the correlation between genetic variation and recalcitrant AD are needed.
屏障或免疫反应相关基因的变异与特应性皮炎（AD）的发生密切相关。本研究旨在确定基因变异和临床特征，以预测“难治性AD”。
将AD患者分为可治疗组和难治性组。可治疗的AD患者通过基础治疗和局部治疗显示出令人满意的临床改善。难治性AD患者由于基础治疗和局部治疗未显示临床改善，使用全身免疫抑制剂超过4周。比较各AD组与对照组之间屏障相关基因（FLG 3321delA、FLG K4022X、KLK7、SPINK 1156、SPINK 1188、SPINK 2475）和免疫反应相关基因（DEFB1、KDR、IL-5RA、IL-9和IL-12RB1a、b）的基因变异频率。
共确定了249例可治疗的AD患者和32例难治性AD患者。KLK7杂合突变（Hetero）在难治性AD患者中比可治疗的AD患者更常见，但无统计学意义。DEFB1杂合突变在可治疗的AD患者中更常见。然而，可治疗和难治性AD之间未观察到其他显著的基因差异。相反，较高的初始湿疹面积严重程度指数（EASI）评分、血清免疫球蛋白E（IgE）水平、屋尘螨变应原特异性IgE和特应性疾病家族史与难治性AD具有统计学意义的相关性。
根据我们的研究，未发现预测难治性AD的基因变异，这表明AD患者的临床表现而非基因变异更可能是预测AD预后的重要因素。需要进一步对基因变异与难治性AD之间的相关性进行大规模研究。
