重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白治疗斑块型银屑病临床疗效相关细胞因子检测
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摘要
目的探讨血清白细胞介素(IL)-12、IL-17A、IL-23和肿瘤坏死因子(TNF)-α水平在重组人Ⅱ型肿瘤坏死因子受体-抗体融合蛋白(商品名益赛普)治疗斑块型银屑病疗效中可能的作用。方法 40例中重度斑块型银屑病患者皮下注射益赛普25 mg/次,2次/周,连续24周;治疗前用酶联免疫吸附法(ELISA)检测患者血清IL-12、IL-17A、IL-23和TNF-α水平。记录治疗前后计算银屑病皮损面积和严重程度指数(PASI)评分。PASI评分较基线下降≥75%定义为临床疗效显著,PASI评分较基线下降<75%定义为临床疗效不显著。根据临床疗效是否显著分为2组,比较2组治疗前血清IL-12、IL-17A、IL-23和TNF-α水平。结果益赛普治疗临床疗效显著组中血清IL-12水平明显高于临床疗效不显著组,差异有统计学意义;2组中IL-17A、IL-23和TNF-α水平差异无统计学意义。结论血清IL-12水平可能是评估益赛普治疗斑块型银屑病临床疗效的一个指标。
Objective In order to investigate the possible role of serum interleukin(IL)-12,IL-17A,IL-23 and tumor necrosis factor(TNF)-α in the treatment of recombinant human tumor necrosis factor receptor type Ⅱ:IgG Fc fusion protein(trade name Etanercept) in patients with plaque psoriasis. Methods Forty moderate to severe plaque-type psoriasis patients were treated with etanercept 25 mg twice a week for 24 weeks. Serum cytokines of IL-12,IL-17A,IL-23 and TNF-α was determined using enzyme-linked immunosorbent assay(ELISA). Psoriasis area and severity indexes(PASI) were calculated before and after etanercept therapy,and achievement of 75% reduction in PASI was defined as the clinical response. Serum cytokines of IL-12,IL-17A,IL-23 and TNF-α was compared between responders and non-responders. Results Baseline IL-12 serum level was significantly higher in responders to etanercept than that in non-responders,while no statistical differences were found between responders and non-responders of IL-17A,IL-23 and TNF-α. Conclusion IL-12 might be a biomarker to predict the clinical response to etanercept in psoriasis.
Objective In order to investigate the possible role of serum interleukin(IL)-12,IL-17A,IL-23 and tumor necrosis factor(TNF)-α in the treatment of recombinant human tumor necrosis factor receptor type Ⅱ:IgG Fc fusion protein(trade name Etanercept) in patients with plaque psoriasis. Methods Forty moderate to severe plaque-type psoriasis patients were treated with etanercept 25 mg twice a week for 24 weeks. Serum cytokines of IL-12,IL-17A,IL-23 and TNF-α was determined using enzyme-linked immunosorbent assay(ELISA). Psoriasis area and severity indexes(PASI) were calculated before and after etanercept therapy,and achievement of 75% reduction in PASI was defined as the clinical response. Serum cytokines of IL-12,IL-17A,IL-23 and TNF-α was compared between responders and non-responders. Results Baseline IL-12 serum level was significantly higher in responders to etanercept than that in non-responders,while no statistical differences were found between responders and non-responders of IL-17A,IL-23 and TNF-α. Conclusion IL-12 might be a biomarker to predict the clinical response to etanercept in psoriasis.
引文
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[10]Park H,Li Z,Yang XO,et al.A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17[J].Nat Immunol,2005,6:1 133-1 141.
[11]Sutton C,Brereton C,Keogh B,et al.A crucial role for interleukin(IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis[J].J Exp Med,2006,203:1 685-1 691.
[2]Nickoloff BJ.Cracking the cytokine code in psoriasis[J].Nat Med,2007,13:242-244.
[3]Sweeney CM,Tobin AM,Kirby B.Innate immunity in the pathogenesis of psoriasis[J].Arch Dermatol Res,2011,303:691-705.
[4]Cabaleiro T,Prieto-Perez R,Navarro R,et al.Paradoxical psoriasiform reactions to anti-TNFalpha drugs are associated with genetic polymorphisms in patients with psoriasis[J].Pharmacogenomics J,2016,16:336-340.
[5]Strober B,Gottlieb A,Leonardi C,et al.Levels of response of psoriasis patients with different baseline characteristics treated with etanercept[J].J Am Acad Dermatol,2006,54:Ab220-Ab220.
[6]Antoniou C,Dessinioti C,Stratigos A,et al.Etanercept in severe,recalcitrant psoriasis:clinical response,safety profile and predictors of response based on a single institution’s experience[J].J Eur A-cad Dermatol Venereol,2009,23:979-982.
[7]de Groot M,Appelman M,Spuls PI,et al.Initial experience with routine administration of etanercept in psoriasis[J].Br J Dermatol,2006,155:808-814.
[9]Hsieh CS,Macatonia SE,Tripp CS,et al.Development of TH1 CD4+T cells through IL-12 produced by Listeria-induced macrophages[J].Science,1993,260:547-549.
[10]Park H,Li Z,Yang XO,et al.A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17[J].Nat Immunol,2005,6:1 133-1 141.
[11]Sutton C,Brereton C,Keogh B,et al.A crucial role for interleukin(IL)-1 in the induction of IL-17-producing T cells that mediate autoimmune encephalomyelitis[J].J Exp Med,2006,203:1 685-1 691.