中华皮肤科杂志 ›› 2021, Vol. 54 ›› Issue (9): 808-813.doi: 10.35541/cjd.20210025

• 论著 • 上一篇    下一篇

外周血流式细胞仪分析在淋巴瘤性红皮病诊断中的作用研究

张莹1    李思琪2    甘璐1    孔英琪1    李颜2    陈浩1    孙建方1   

  1. 1中国医学科学院、北京协和医学院皮肤病医院病理科，南京  210042；2模式动物与疾病研究教育部重点实验室  医药生物技术国家重点实验室  化学和生物医药创新研究院 南京大学医学院模式动物研究所，南京  210061
  • 收稿日期:2021-01-11 修回日期:2021-06-28 发布日期:2021-09-02
  • 通讯作者: 陈浩;孙建方 E-mail:ch76ch@163.com; fangmin5758@aliyun.com
  • 基金资助:
    中国医学科学院医学与健康科技创新工程项目（CIFMS-2017-I2M-1-017）；江苏省六大高峰人才项目（WSN-030）；南京市国家级临床医学中心培育计划项目（2019060001）；北京协和医学院研究生创新基金项目（3301030202030）

Role of flow cytometric analysis of peripheral blood in the diagnosis of lymphoma-associated erythroderma

Zhang Ying1, Li Siqi2, Gan Lu1, Kong Yingqi1, Li Yan2, Chen Hao1, Sun Jianfang1   

  1. 1Department of Pathology, Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing 210042, China; 2The State Key Laboratory of Pharmaceutical Biotechnology, Chemistry and Biomedicine Innovation Center/Model Animal Research Center, Nanjing University, Nanjing 210061, China
  • Received:2021-01-11 Revised:2021-06-28 Published:2021-09-02
  • Contact: Chen Hao; Sun Jianfang E-mail:ch76ch@163.com; fangmin5758@aliyun.com
  • Supported by:
    CAMS Innovation Fund for Medical Sciences （CIFMS-2017-I2M-1-017）; Six Major Talent Summit in Jiangsu Province （WSN-030）; Nanjing Incubation Program for National Clinical Research Center （2019060001）; Peking Union Medical College Innovation Fund for Postgraduates （3301030202030）

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摘要： 【摘要】 目的 探讨外周血流式细胞仪检测在红皮病诊断中的应用价值。方法 收集2017年9月至2020年12月在中国医学科学院皮肤病医院就诊的29例红皮病患者，包括6例红皮病型蕈样肉芽肿（EMF）、5例Sézary综合征（SS）及18例不同病因的炎症性红皮病（IE），4例健康志愿者为健康对照。采用流式细胞仪检测外周血淋巴细胞亚群、免疫表型及克隆性，比较其在炎症性红皮病与淋巴瘤相关红皮病的差异。采用单因素方差分析及LSD-t检验进行组间比较。结果 4组受试者的T细胞、B细胞、NK细胞及CD4-CD8-细胞比例差异均有统计学意义（均P < 0.001），SS患者T细胞比例（93.8% ± 3.4%）高于EMF（42.7% ± 6.4%）及IE（46.0% ± 6.8%，t = 12.8、14.4， P < 0.001），IE患者CD4-CD8-细胞比例（0.37% ± 0.40%）低于EMF（2.93% ± 0.84%）及SS（2.38% ± 0.74%，t = 9.2、6.7， P < 0.05）。健康对照及IE患者均未检测到克隆性T细胞受体可变区β链（TCR-vβ）表达；3例 EMF及所有SS患者检测到表达克隆性TCR-vβ的细胞亚群，且TCR-vβ克隆性细胞均为CD4+CD7-CD26-表型。4组受试者CD4+ T淋巴细胞表面表达趋化因子受体CCR4、CXCR3、CCR5与皮肤淋巴细胞抗原（CLA）及程序性死亡受体1（PD-1）的细胞比例差异均有统计学意义（均P < 0.001），IE患者表达CCR4、CLA、PD-1细胞比例低于SS及EMF患者（均P < 0.001），表达CXCR3、CCR5细胞比例高于SS患者及EMF患者 （均P < 0.001）。 结论 流式细胞仪检测外周血淋巴细胞亚群、免疫表型及克隆性，可为红皮病患者的病因诊断提供佐证，有助于淋巴瘤相关红皮病与炎症性红皮病的鉴别诊断。

关键词: 淋巴瘤, T细胞, 皮肤, Sézary综合征, 流式细胞术, 红皮病型蕈样肉芽肿, 炎症性红皮病, T淋巴细胞, 表位, T淋巴细胞, T细胞受体可变区β链

Abstract: 【Abstract】 Objective To investigate the value of flow cytometric analysis of peripheral blood in the diagnosis of erythroderma. Methods A total of 29 patients with erythroderma were collected from Hospital of Dermatology, Chinese Academy of Medical Sciences from September 2017 to December 2020, including 6 with erythrodermic mycosis fungoides （EMF）, 5 with Sézary syndrome （SS）, 18 with inflammatory erythroderma （IE） with different etiologies. Four healthy volunteers served as healthy controls. Flow cytometry was performed to detect peripheral blood lymphocyte subsets, immunophenotypes and clonality, and their differences were analyzed between inflammatory erythroderma and lymphoma-related erythroderma. One-way analysis of variance and least significant difference-t test were used for comparisons between groups. Results The proportions of T cells, B cells, NK cells and CD4-CD8- cells significantly differed among the EMF group, SS group, IE group and control group （all P < 0.001）. The proportion of T cells was significantly higher in the SS group （93.8% ± 3.4%） than in the EMF group （42.7% ± 6.4%） and IE group （46.0% ± 6.8%, t = 12.8, 14.4, respectively, both P < 0.001）, and the proportion of CD4-CD8- cells was significantly lower in the IE group （0.37% ± 0.40%） than in the EMF group （2.93% ± 0.84%） and SS group （2.38% ± 0.74%, t = 9.2, 6.7, respectively, both P < 0.05）. The expression of clonal T-cell receptor β-chain variable region （TCR-vβ） was not detected in healthy controls or IE patients; the T cell subsets expressing clonal TCR-vβ were detected in 3 cases of EMF and all cases of SS, and they were all identified to be cells with a CD4+CD7-CD26- phenotype. There were significant differences among the above 4 groups of subjects in the proportions of CD4+ T lymphocytes expressing chemokine receptors CCR4, CXCR3, CCR5, cutaneous lymphocyte antigen （CLA） or programmed death receptor-1 （PD-1） on the cell surface （all P < 0.001）. Compared with the SS group and EMF group, the IE group showed significant decreased proportions of CD4+ T lymphocytes expressing CCR4, CLA or PD-1 （all P < 0.001）, but significantly increased proportions of CD4+ T lymphocytes expressing CXCR3 or CCR5 （all P < 0.001）. Conclusion Flow cytometric analysis of peripheral blood lymphocyte subsets, immunophenotypes and clonality can provide a reference for the etiological diagnosis of erythroderma, and is helpful for the differential diagnosis between lymphoma-associated erythroderma and inflammatory erythroderma.

Key words: Lymphoma, T-cell, cutaneous, Sézary syndrome, Flow cytometry, Erythrodermic mycosis fungoides, Inflammatory erythroderma, T-lymphocytes, Epitopes, T-lymphocyte, T-cell receptor β-chain variable region