蕈样肉芽肿白介素-13及其受体的表达与意义

发布时间：2018-06-28 02:41

  本文选题：蕈样肉芽肿 + 细胞转化　； 参考：《安徽医科大学》2017年硕士论文

【摘要】：背景蕈样肉芽肿(MF)是最常见的皮肤淋巴瘤,约占皮肤T淋巴瘤的50%。MF区别于其他类型皮肤淋巴瘤的一个最显著特征,是其具有相对惰性的生物学行为,即临床表现为斑片乃至斑块的皮损进展极其缓慢,可持续数年至数十年不等。然而,一旦出现进展期皮损如斑块或肿瘤,则显示显著的侵袭性生物学行为,包括累及外周血、淋巴结或内脏器官。探寻一种能够预判MF生物学行为转化的标志物,对MF的临床管理和治疗选择极其重要。IL-13作为Th2相关细胞因子,可以直接促进肿瘤增殖和/或协同抑制肿瘤免疫监视的作用;而其受体IL-13Rα1及IL-13Rα2是一种新近发现的血源性受体家族成员之一,与IL-13具有相对高度专一的亲和力,有待成为特异性的、有前途的肿瘤基因治疗靶点。目的本研究通过检测分析不同时期MF患者皮损中IL-13及其受体的表达,以期为MF生物学行为转化与进展提供一种新的标记和候选的分子治疗靶点。方法收集杭州市第三人民医院皮肤科2010年1月-2016年3月经临床、病理、免疫表型和/或T细胞受体基因重排检测确诊的MF石蜡组织标本34例,根据TNM分期分为ⅠA期5例,ⅠB期9例,ⅡA期17例和ⅡB期3例。另外选择正常皮肤组织10例作为对照。应用免疫组化方法分别检测IL-13、IL-13Rα1及IL-13Rα2的表达。另外,应用MTS法检测加入不同浓度IL-13后MF细胞株Hut-102细胞的吸光度值,分析IL-13对Hut-102细胞的增殖作用;应用流式细胞术检测加入IL-13后Hut-102细胞周期的变化。结果IL-13、IL-13Rα1和IL-13Rα2表达于各期MF皮损组织的异型淋巴样细胞和亲表皮性淋巴样细胞,尤其IL-13Rα2几乎高表达于所有的MF皮损组织。正常皮肤组织及淋巴细胞均不表达IL-13及其受体。随着MF病程的进展,皮损组织IL-13及其受体表达率升高。Ⅰ期MF皮损IL-13、IL-13Rα1及IL-13Rα2的表达率均显著低于Ⅱ期MF皮损,差异均有统计学意义(Ⅰ、Ⅱ期MF皮损IL-13的表达率分别为10.00±3.14、27.50±11.00,P0.05;Ⅰ、Ⅱ期MF皮损IL-13Rα1的表达率分别为21.43±6.88、39.45±9.43,P0.05;Ⅰ、Ⅱ期MF皮损IL-13Rα2的表达率分别为31.14±6.38、44.40±11.15,P0.05),但在ⅠA期与ⅠB期之间以及ⅡA期与ⅡB期之间差异均没有统计学意义(均P0.05)。IL-13对体外培养的Hut-102细胞有明显的增殖促进作用,且会随着剂量的增大产生的促进作用增强。流式细胞术结果显示50ng/ml浓度以上的IL-13均可使Hut-102细胞G0/G1期细胞比例减少,位与S期的细胞比例增多,而对G2/M期无明显影响。结论IL-13及其受体尤其是IL-13Rα2,有期成为MF早期诊断和生物学行为预判的标志物。IL-13对体外培养的Hut-102细胞有促进增殖的作用,能使促进其尽快从G0/G1期进入S期。
[Abstract]:Background mycosis fungoides (MF) is the most common cutaneous lymphoma, accounting for about 50% of cutaneous T lymphoma. MF is one of the most prominent characteristics of other types of cutaneous lymphoma, and it has relatively inert biological behavior. That is, the clinical manifestations of plaque and plaque skin damage progress is extremely slow, lasting from several years to decades. However, the presence of advanced lesions such as plaques or tumors shows significant invasive biological behavior, including the involvement of peripheral blood, lymph nodes, or visceral organs. To explore a biomarker that can predict the biological behavior transformation of MF, IL-13 is extremely important for the clinical management and treatment selection of MF as Th2-related cytokines, which can directly promote tumor proliferation and / or synergistic inhibition of tumor immune surveillance. The receptor IL-13R 伪 1 and IL-13R 伪 2 are one of the newly discovered members of the hematogenous receptor family, and have a relatively high affinity to IL-13, so it needs to be a specific and promising target for tumor gene therapy. Objective to detect and analyze the expression of IL-13 and its receptor in skin lesions of MF patients at different stages in order to provide a new marker and candidate molecular therapeutic target for the biological behavior transformation and progression of MF. Methods from January 2010 to March 2016, 34 cases of MF paraffin tissues confirmed by pathological examination, immunophenotype and / or T cell receptor gene rearrangement were collected and divided into stage 鈪，

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