Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response.
Reversal of atopic dermatitis with narrow-band UVB phototherapy and biomarkers for therapeutic response.
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DOI：
10.1016/j.jaci.2011.05.042
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发表时间：
2011-09
期刊：
影响因子：
--
通讯作者：
Guttman-Yassky E
中科院分区：
文献类型：
--
作者：
Tintle S;Shemer A;Suárez-Fariñas M;Fujita H;Gilleaudeau P;Sullivan-Whalen M;Johnson-Huang L;Chiricozzi A;Cardinale I;Duan S;Bowcock A;Krueger JG;Guttman-Yassky E
特应性皮炎(AD)是一种常见的炎症性皮肤病，主要表现为Th2/T22免疫激活和表皮屏障缺陷。窄带UVB(NB-UVB)被认为是治疗中重度AD的有效方法。在银屑病中，已经发现NB-UVB可以抑制Th1/Th17极化，从而逆转表皮增生。在AD患者中，这种治疗的免疫调节作用在很大程度上是未知的。评价NB-UVB对AD患者免疫和屏障功能异常的影响，旨在建立疾病的可逆性和治疗反应的生物标志物。12例中重度慢性AD患者接受NB-UVB光疗，每周3次，共12周。治疗前后分别采集皮损和非皮损皮肤活检标本，并通过基因表达和免疫组织化学研究进行评价。所有患者接受NB-UVB光疗后，AD(SCORAD)指数评分至少降低50%。Th2、T22和Th1免疫通路被抑制，表皮增殖和分化指标正常化。疾病活动度的逆转与炎性白细胞、Th2/“T22”相关细胞因子和趋化因子的消除以及屏障蛋白的正常表达有关。我们的研究表明，慢性AD患者临床疾病的缓解伴随着表皮缺陷和潜在的免疫激活的逆转。我们定义了一组疾病反应的生物标志物，将慢性AD患者中消退的Th2和“T22”炎症与屏障病理逆转联系在一起。通过广泛的免疫靶向治疗显示AD表皮表型的逆转，我们的数据反对固定的遗传表型。
Atopic dermatitis (AD) is a common inflammatory skin disease exhibiting a predominantly Th2/“T22” immune activation and a defective epidermal barrier. Narrow-band UVB (NB-UVB) is considered an efficient treatment for moderate-to-severe AD. In psoriasis, NB-UVB has been found to suppress the Th1/Th17-polarization with subsequent reversal of epidermal hyperplasia. The immunomodulatory effects of this treatment are largely unknown in AD. To evaluate the effects of NB-UVB on immune and barrier abnormalities in AD, aiming to establish reversibility of disease and biomarkers of therapeutic response. 12 moderate-to-severe chronic AD patients received NB-UVB phototherapy 3 times weekly for up to 12 weeks. Lesional and non-lesional skin biopsies were obtained before and after treatment and evaluated by gene-expression and immunohistochemistry studies. All patients had at least a 50% reduction in SCORing of AD (SCORAD) index with NB-UVB phototherapy. The Th2, “T22,” and Th1 immune pathways were suppressed and measures of epidermal hyperplasia and differentiation normalized. The reversal of disease activity was associated with elimination of inflammatory leukocytes, Th2/“T22”- associated cytokines and chemokines, and normalized expression of barrier proteins. Our study shows that resolution of clinical disease in patients with chronic AD is accompanied by reversal of both the epidermal defects and the underlying immune activation. We have defined a set of biomarkers of disease response that associate resolved Th2 and “T22” inflammation in chronic AD patients with reversal of barrier pathology. By showing reversal of the AD epidermal phenotype with a broad immune-targeted therapy, our data argues against a fixed genetic phenotype.
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