Mitsuishi K, Nakamura T, Sakata Y, Yuyama N, Arima K, Sugita Y, Suto H, Izuhara K, Ogawa H
Department of Dermatology, Atopy (Allergy) Research Center, Juntendo University, Tokyo, Japan.
Clin Exp Allergy. 2005 Oct;35(10):1327-33. doi: 10.1111/j.1365-2222.2005.02353.x.
Although it is thought that both Th1- and Th2-type inflammations are involved in the pathogenesis of atopic dermatitis (AD), it is controversial which immune response is more involved in regulating the clinical severity of AD. We recently found that the squamous cell carcinoma antigens 1 (SCCA1) and SCCA2 are novel biomarkers of bronchial asthma, downstream of IL-4 and IL-13.
We examined whether SCCA1 and SCCA2 could also serve as biomarkers of AD, reflecting its Th2-type immune responses, and whether the expression level of SCCA was correlated with clinical severity of AD.
We compared the expression of SCCA1 and SCCA2 at the mRNA and protein levels in both involved and uninvolved skin of AD patients and in normal control skin. We next analysed induction of SCCA by IL-4 or IL-13 in keratinocytes. Finally, we compared the serum level of SCCA with laboratory parameters reflecting Th2-type inflammation and clinical severity in AD patients.
SCCA1 and SCCA2 were highly expressed in involved skin of AD patients, compared with their uninvolved skin, at both mRNA and protein levels. SCCA protein was dominantly expressed in suprabasal keratinocytes in the epidermis of AD patients. Either IL-4 or IL-13, but not IFN-gamma or TNF, induced production of SCCA in keratinocytes. These result suggest that SCCA is induced in AD skin, probably due to direct actions of IL-4 and/or IL-13 on keratinocytes. Serum levels of SCCA were well correlated with eosinophil numbers and serum lactate dehydrogenase levels, and weakly with serum IgE levels, in AD patients. Furthermore, serum levels of SCCA were strongly correlated with clinical severity.
Th2-type inflammation dominantly regulates the clinical severity of AD, and SCCA is a relevant biomarker of AD, reflecting both Th2-type inflammation and clinical severity.
尽管认为Th1型和Th2型炎症均参与特应性皮炎（AD）的发病机制，但哪种免疫反应在调节AD的临床严重程度中起更大作用仍存在争议。我们最近发现，鳞状细胞癌抗原1（SCCA1）和SCCA2是支气管哮喘的新型生物标志物，位于IL-4和IL-13的下游。
我们研究了SCCA1和SCCA2是否也可作为AD的生物标志物，反映其Th2型免疫反应，以及SCCA的表达水平是否与AD的临床严重程度相关。
我们比较了AD患者受累皮肤和未受累皮肤以及正常对照皮肤中SCCA1和SCCA2在mRNA和蛋白质水平的表达。接下来，我们分析了角质形成细胞中IL-4或IL-13对SCCA的诱导作用。最后，我们比较了AD患者血清中SCCA水平与反映Th2型炎症和临床严重程度的实验室参数。
与未受累皮肤相比，AD患者受累皮肤中SCCA1和SCCA2在mRNA和蛋白质水平均高表达。SCCA蛋白主要表达于AD患者表皮的基底上层角质形成细胞中。IL-4或IL-13均可诱导角质形成细胞产生SCCA，但IFN-γ或TNF则不能。这些结果表明，AD皮肤中SCCA的诱导可能是由于IL-4和/或IL-13对角质形成细胞的直接作用。在AD患者中，血清SCCA水平与嗜酸性粒细胞数量和血清乳酸脱氢酶水平密切相关，与血清IgE水平相关性较弱。此外，血清SCCA水平与临床严重程度密切相关。
Th2型炎症主要调节AD的临床严重程度，SCCA是AD的相关生物标志物，反映Th2型炎症和临床严重程度。
