利妥昔单抗通过降低IL-17及诱导肥大细胞凋亡治疗原发干燥综合征
发表者：金银姬
日期：2015-02-27
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摘要：目的：本研究的目的是评估利妥昔单抗（RTX）在原发性干燥综合征（pSS）患者唾液腺中IL-17/IL-23通路表达的调节作用
方法：获取15名pSS患者RTX使用前及使用后1年的唾液腺活检标本。通过免疫组化方法评估RTX使用前及使用后唾液腺IL-17,、IL-23p19及p-STAT3表达。同时进行体外实验研究pSS患者中肥大细胞对Th17应答的调节作用及RTX在肥大细胞中的免疫学效应。
结果：在pSS患者唾液腺中IL-17主要通过T细胞及肥大细胞过表达。经过RTX治疗后，IL-17在唾液腺中的表达明显减少，同时肥大细胞显著减少，而IL-23p19及p-STAT3的表达无改变。异质性外周淋巴细胞的体外实验结果表明，RTX可诱导孤立性肥大细胞的凋亡。最后，从pSS患者外周血单个核细胞（PBMC）中分离的肥大细胞中Th17细胞显著增加。
结论：在pSS患者中，RTX通过减少IL-17的表达及诱导肥大细胞的凋亡起作用。
附原文：Objective. The aim of this study was to evaluate the role of rituximab (RTX) in modulating the expression of the IL-17/IL-23 pathway in the salivary glands (SGs) of patients with primary SS (pSS).Methods. Consecutive SG biopsies were obtained from 15 patients with pSS before and after 1 year of RTX therapy. The SG expression of IL-17, IL-23p19 and p-STAT3 was evaluated by immunohistochemistry at baseline and after RTX therapy. The role of mast cells in pSS patients in modulating the Th17 response and the immunologic effect of RTX on mast cells were also studied in in vitro experiments.Results. IL-17 was overexpressed in the SGs of patients with pSS mainly by infiltrating T cells and mastcells. After RTX therapy, the SG expression of IL-17, but not of IL-23p19 and p-STAT3, was significantlyreduced and was accompanied by the depletion of tissue mast cells. In in vitro experiments with heterologous peripheral lymphocytes RTX significantly induced the apoptosis of isolated mast cells. Finally, mast cells isolated from peripheral blood mononuclear cells of pSS patients in vitro significantly increased Th17 lymphocytes.Conclusion. RTX acts on pSS patients by globally reducing the expression of IL-17 and specifically inducing a pronounced apoptotic depletion of mast cells.
引自：Francesco Ciccia, Giuliana Guggino, Aroldo Rizzo, Riccardo Alessandro,Francesco Carubbi, AnnaRita Giardina, Paola Cipriani, Angelo Ferrante,Alessandra Cannizzaro, Roberto Giacomelli and Giovanni Triolo. Rituximab modulates IL-17 expression in the salivary glands of patients with primary Sjo¨ gren’s syndrome. Rheumatology. 2014 Mar 6. doi:10.1093/rheumatology/keu004 （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）
方法：获取15名pSS患者RTX使用前及使用后1年的唾液腺活检标本。通过免疫组化方法评估RTX使用前及使用后唾液腺IL-17,、IL-23p19及p-STAT3表达。同时进行体外实验研究pSS患者中肥大细胞对Th17应答的调节作用及RTX在肥大细胞中的免疫学效应。
结果：在pSS患者唾液腺中IL-17主要通过T细胞及肥大细胞过表达。经过RTX治疗后，IL-17在唾液腺中的表达明显减少，同时肥大细胞显著减少，而IL-23p19及p-STAT3的表达无改变。异质性外周淋巴细胞的体外实验结果表明，RTX可诱导孤立性肥大细胞的凋亡。最后，从pSS患者外周血单个核细胞（PBMC）中分离的肥大细胞中Th17细胞显著增加。
结论：在pSS患者中，RTX通过减少IL-17的表达及诱导肥大细胞的凋亡起作用。
附原文：Objective. The aim of this study was to evaluate the role of rituximab (RTX) in modulating the expression of the IL-17/IL-23 pathway in the salivary glands (SGs) of patients with primary SS (pSS).Methods. Consecutive SG biopsies were obtained from 15 patients with pSS before and after 1 year of RTX therapy. The SG expression of IL-17, IL-23p19 and p-STAT3 was evaluated by immunohistochemistry at baseline and after RTX therapy. The role of mast cells in pSS patients in modulating the Th17 response and the immunologic effect of RTX on mast cells were also studied in in vitro experiments.Results. IL-17 was overexpressed in the SGs of patients with pSS mainly by infiltrating T cells and mastcells. After RTX therapy, the SG expression of IL-17, but not of IL-23p19 and p-STAT3, was significantlyreduced and was accompanied by the depletion of tissue mast cells. In in vitro experiments with heterologous peripheral lymphocytes RTX significantly induced the apoptosis of isolated mast cells. Finally, mast cells isolated from peripheral blood mononuclear cells of pSS patients in vitro significantly increased Th17 lymphocytes.Conclusion. RTX acts on pSS patients by globally reducing the expression of IL-17 and specifically inducing a pronounced apoptotic depletion of mast cells.
引自：Francesco Ciccia, Giuliana Guggino, Aroldo Rizzo, Riccardo Alessandro,Francesco Carubbi, AnnaRita Giardina, Paola Cipriani, Angelo Ferrante,Alessandra Cannizzaro, Roberto Giacomelli and Giovanni Triolo. Rituximab modulates IL-17 expression in the salivary glands of patients with primary Sjo¨ gren’s syndrome. Rheumatology. 2014 Mar 6. doi:10.1093/rheumatology/keu004 （注：干燥综合症病人或亲属可加QQ群交流，群号： 118194945 ，本网站站长私人微信号： ssgzz88 ）