Boonk Stephanie E, Zoutman Willem H, Marie-Cardine Anne, van der Fits Leslie, Out-Luiting Jacoba J, Mitchell Tracey J, Tosi Isabella, Morris Stephen L, Moriarty Blaithin, Booken Nina, Felcht Moritz, Quaglino Pietro, Ponti Renata, Barberio Emanuela, Ram-Wolff Caroline, Jäntti Kirsi, Ranki Annamari, Bernengo Maria Grazia, Klemke Claus-Detlev, Bensussan Armand, Michel Laurence, Whittaker Sean, Bagot Martine, Tensen Cornelis P, Willemze Rein, Vermeer Maarten H
Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.
J Invest Dermatol. 2016 Jul;136(7):1364-1372. doi: 10.1016/j.jid.2016.01.038. Epub 2016 Feb 28.
Differentiation between Sézary syndrome and erythrodermic inflammatory dermatoses can be challenging, and a number of studies have attempted to identify characteristic immunophenotypic changes and molecular biomarkers in Sézary cells that could be useful as additional diagnostic criteria. In this European multicenter study, the sensitivity and specificity of these immunophenotypic and recently proposed but unconfirmed molecular biomarkers in Sézary syndrome were investigated. Peripheral blood CD4(+) T cells from 59 patients with Sézary syndrome and 19 patients with erythrodermic inflammatory dermatoses were analyzed for cell surface proteins by flow cytometry and for copy number alterations and differential gene expression using custom-made quantitative PCR plates. Experiments were performed in duplicate in two independent centers using standard operating procedures with almost identical results. Sézary cells showed MYC gain (40%) and MNT loss (66%); up-regulation of DNM3 (75%), TWIST1 (69%), EPHA4 (66%), and PLS3 (66%); and down-regulation of STAT4 (91%). Loss of CD26 (≥80% CD4(+) T cells) and/or CD7 (≥40% CD4(+) T cells) and combination of altered expression of STAT4, TWIST1, and DNM3 or PLS3 could distinguish, respectively, 83% and 98% of patients with Sézary syndrome from patients with erythrodermic inflammatory dermatoses with 100% specificity. These additional diagnostic panels will be useful adjuncts in the differential diagnosis of Sézary syndrome versus erythrodermic inflammatory dermatoses.
蕈样肉芽肿综合征（Sézary syndrome）与红皮病型炎症性皮肤病的鉴别诊断颇具挑战性，许多研究试图确定蕈样肉芽肿细胞中具有特征性的免疫表型变化和分子生物标志物，这些标志物可用作额外的诊断标准。在这项欧洲多中心研究中，对这些免疫表型以及最近提出但尚未得到证实的蕈样肉芽肿综合征分子生物标志物的敏感性和特异性进行了研究。采用流式细胞术分析了59例蕈样肉芽肿综合征患者和19例红皮病型炎症性皮肤病患者外周血CD4(+) T细胞的细胞表面蛋白，并使用定制的定量PCR板分析了拷贝数改变和差异基因表达。实验在两个独立中心重复进行，采用标准操作程序，结果几乎相同。蕈样肉芽肿细胞显示MYC基因扩增（40%）和MNT基因缺失（66%）；DNM3（75%）、TWIST1（69%）、EPHA4（66%）和PLS3（66%）上调；STAT4（91%）下调。CD26缺失（≥80% CD4(+) T细胞）和/或CD7缺失（≥40% CD4(+) T细胞）以及STAT4、TWIST1和DNM3或PLS3表达改变的组合，分别可以将83%和98%的蕈样肉芽肿综合征患者与红皮病型炎症性皮肤病患者区分开来，特异性为100%。这些额外的诊断指标将有助于蕈样肉芽肿综合征与红皮病型炎症性皮肤病的鉴别诊断。
