van Duijnhoven M W F M, Körver J E M, Vissers W H P M, van Vlijmen-Willems I M J J, Pasch M C, van Erp P E J, Van de Kerkhof P C M
Department of Dermatology, UMC St Radboud, Nijmegen, the Netherlands.
J Eur Acad Dermatol Venereol. 2006 Jan;20(1):27-33. doi: 10.1111/j.1468-3083.2005.01322.x.
The effect of the established antipsoriatic treatment with topical calcipotriol (with a maximum of 100 g per week) in addition to systemic treatment with alefacept, a new biological agent for psoriasis, on epidermal cell populations in the psoriatic lesion was investigated using a combination of the Zenon labelling technique and microscopic image analysis. Epidermal cell populations were measured quantitatively with this sensitive method.
PATIENTS/METHODS: Frozen sections of non-treated psoriatic epidermis and psoriatic epidermis treated with either alefacept intramuscular or alefacept intramuscular in combination with topical calcipotriol for 12 weeks were compared immunohistochemically. Antibodies against keratin 6, 10 and 15 were labelled with the Zenon technique, whereas antibodies against the Ki-67 antigen and beta-1 integrin were covalently Fluorescein Isothiocyanate (FITC)-labelled. Using image analysis, these markers were measured in the epidermis in a standardized manner.
Treatment of psoriasis with alefacept resulted in a good clinical response in several patients and in a normalization of epidermal expression of the immunohistochemical parameters for differentiation and proliferation. The addition of topical calcipotriol resulted in a faster clinical improvement with a similar overall clinical response and a similar response of epidermal cell populations as compared to treatment with alefacept monotherapy after 12 weeks of treatment. This study also suggests that the appearance of keratin 15 has a predictive value for the duration of remission. It can be concluded that the addition of a low-dose calcipotriol treatment does not contribute to the clinical efficacy of alefacept, both at the clinical level and with respect to markers for epidermal proliferation and differentiation.
采用Zenon标记技术与显微图像分析相结合的方法，研究已确立的外用卡泊三醇（每周最大剂量100 g）联合新型银屑病生物制剂阿法赛特进行系统治疗，对银屑病皮损中表皮细胞群体的影响。用这种灵敏的方法对表皮细胞群体进行定量测定。
患者/方法：对未经治疗的银屑病表皮以及分别接受肌肉注射阿法赛特或肌肉注射阿法赛特联合外用卡泊三醇治疗12周后的银屑病表皮的冰冻切片进行免疫组织化学比较。用Zenon技术标记抗角蛋白6、10和15的抗体，而抗Ki-67抗原和β-1整合素的抗体则用异硫氰酸荧光素（FITC）共价标记。使用图像分析，以标准化方式在表皮中测量这些标志物。
用阿法赛特治疗银屑病使部分患者获得了良好的临床反应，并使分化和增殖的免疫组织化学参数的表皮表达恢复正常。与阿法赛特单药治疗12周后的情况相比，加用外用卡泊三醇可使临床改善更快，总体临床反应相似，表皮细胞群体的反应也相似。本研究还表明，角蛋白15的出现对缓解期持续时间具有预测价值。可以得出结论，无论在临床水平还是在表皮增殖和分化标志物方面，加用低剂量卡泊三醇治疗均未提高阿法赛特的临床疗效。
