Daridon Capucine, Burmester Gerd R, Dörner Thomas
Department of Rheumatology and Clinical Immunology, Charité University Medicine Berlin and Deutsches, Rheumaforschungszentrum, Berlin 10098, Germany.
Curr Opin Rheumatol. 2009 May;21(3):205-10. doi: 10.1097/BOR.0b013e32832a0760.
To evaluate the impact of particular anticytokine therapies able to indirectly target B cells with emphasis on the tumor necrosis factor (TNF) family members, B cell activating factor/B lymphocyte stimulator (BAFF/BLyS) and a proliferation-inducing ligand (APRIL).
Although blockade of TNF/lymphotoxin by etanercept has been shown to have an impact on memory B cells, recent studies of inhibiting the TNF family members BAFF/BlyS or simultaneously blocking BAFF/BlyS and APRIL in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) clearly demonstrated biologic activity, including reductions of immunoglobulin levels. However, clear evidence of clinical activity by any of the compounds interfering with BAFF/BLys or APRIL has not yet been shown.
Although anticytokine therapies mainly blocking signaling pathways of innate immunity, that is TNF-alpha, have shown efficacy in the treatment of arthritides and have partial effects on memory B cells, current studies evaluate effects on adaptive immunity by blocking BAFF/BlyS and/or APRIL which indirectly act on B and plasma cells.
评估能够间接靶向B细胞的特定抗细胞因子疗法的影响,重点关注肿瘤坏死因子(TNF)家族成员、B细胞活化因子/B淋巴细胞刺激因子(BAFF/BLyS)和增殖诱导配体(APRIL)。
尽管已证明依那西普阻断TNF/淋巴毒素对记忆B细胞有影响,但近期在类风湿关节炎(RA)和系统性红斑狼疮(SLE)中抑制TNF家族成员BAFF/BlyS或同时阻断BAFF/BlyS和APRIL的研究清楚地证明了其生物学活性,包括免疫球蛋白水平降低。然而,尚未显示任何干扰BAFF/BLys或APRIL的化合物具有临床活性的确切证据。
尽管抗细胞因子疗法主要阻断固有免疫的信号通路,即TNF-α,已在关节炎治疗中显示出疗效并对记忆B细胞有部分作用,但目前的研究通过阻断间接作用于B细胞和浆细胞的BAFF/BlyS和/或APRIL来评估对适应性免疫的影响。