Schindler Mandana, Drozdenko Gennadiy, Kühl Anja Andrea, Worm Margitta
Allergy Center Charité, Department of Dermatology and Allergology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Int Arch Allergy Immunol. 2014;165(1):18-26. doi: 10.1159/000365659. Epub 2014 Sep 27.
Oral alitretinoin (9-cis-retinoic acid; 9-cis-RA) has shown clinical efficacy in patients with chronic hand eczema (CHE). Herein, we investigated the impact of oral 9-cis-RA on the local and systemic immune response in patients with CHE.
Twenty patients with CHE were treated with oral alitretinoin (10 or 30 mg/day) for at least 24 weeks. Blood samples were taken for flow cytometry, and serum samples were assessed by ELISA to determine immunoglobulin (Ig) levels. Skin biopsies from lesional skin were evaluated immunohistochemically.
Upon 9-cis-RA treatment, improvement of the CHE was observed in all patients. A significant decrease in plasmablasts in the peripheral blood and a significant reduction of serum IgE levels were determined. Furthermore, we detected a significant reduction of CD4+ cells and regulatory T cells in the peripheral blood upon treatment. By contrast, these cell subsets were significantly increased in the affected skin. Cytokine analysis of activated CD154-positive T cells showed a reduction of interleukin (IL)-17 but not of IL-4 or IFN-γ production.
Overall, our data indicate a disease-modifying effect of 9-cis-RA, including a systemic decrease in IL-17-positive cells, but decreased serum IgE and CD23 expression. The increased frequency of FoxP3-positive cells in the skin upon treatment may suggest a mechanism by which hand eczema is therapeutically targeted by 9-cis-RA, but this will need to be proven in the future studies.
口服阿利特维甲酸(9-顺式维甲酸;9-cis-RA)已在慢性手部湿疹(CHE)患者中显示出临床疗效。在此,我们研究了口服9-cis-RA对CHE患者局部和全身免疫反应的影响。
20例CHE患者接受口服阿利特维甲酸(10或30mg/天)治疗至少24周。采集血样进行流式细胞术检测,并通过ELISA评估血清样本以确定免疫球蛋白(Ig)水平。对病变皮肤进行皮肤活检,采用免疫组织化学方法进行评估。
经9-cis-RA治疗后,所有患者的CHE均有改善。外周血中浆母细胞显著减少,血清IgE水平显著降低。此外,治疗后外周血中CD4+细胞和调节性T细胞显著减少。相比之下,这些细胞亚群在受累皮肤中显著增加。对活化的CD154阳性T细胞进行细胞因子分析显示,白细胞介素(IL)-17产生减少,但IL-4或干扰素-γ产生未减少。
总体而言,我们的数据表明9-cis-RA具有疾病改善作用,包括全身IL-17阳性细胞减少,但血清IgE和CD23表达降低。治疗后皮肤中FoxP3阳性细胞频率增加可能提示9-cis-RA治疗手部湿疹的一种机制,但这需要在未来的研究中得到证实。