Stohl William
University of Southern California Keck School of Medicine, Division of Rheumatology , 2011 Zonal Ave. HMR 711, Los Angeles, CA 90033 , USA +1 323 442 1959 ; +1 323 442 2874 ;
Expert Opin Ther Targets. 2014 Apr;18(4):473-89. doi: 10.1517/14728222.2014.888415. Epub 2014 Feb 13.
The B-cell activating factor (BAFF) axis comprises two ligands (BAFF and APRIL) and three receptors (BCMA, TACI, BR3). BAFF is a vital B-cell survival factor and overexpression of BAFF in both mice and humans is associated with systemic lupus erythematosus (SLE). The anti-BAFF monoclonal antibody (mAb), belimumab, was recently approved by the US FDA for the treatment of adult SLE patients, and three additional BAFF antagonists (atacicept, blisibimod, tabalumab) are presently being evaluated in SLE Phase-III trials.
The general biological properties of the individual elements of the BAFF/APRIL axis are reviewed, with emphasis placed on molecular interactions and the potential relevance of each individual element to SLE.
The success of belimumab, an agent which promotes only modest B-cell depletion, is contrasted with the failure of the anti-CD20 mAb rituximab, an agent which promotes profound B-cell depletion, and multiple arguments are offered to explain this apparent paradox. Real and perceived limitations to belimumab therapy are presented, and possibilities for other therapeutic agents that target specific elements of the BAFF/APRIL axis are discussed.
B细胞活化因子（BAFF）轴由两种配体（BAFF和APRIL）和三种受体（BCMA、TACI、BR3）组成。BAFF是一种重要的B细胞存活因子，在小鼠和人类中BAFF的过表达均与系统性红斑狼疮（SLE）相关。抗BAFF单克隆抗体（mAb）贝利尤单抗最近被美国食品药品监督管理局（FDA）批准用于治疗成年SLE患者，另外三种BAFF拮抗剂（阿他西普、布利西莫德、塔巴单抗）目前正在SLE的III期试验中进行评估。
本文综述了BAFF/APRIL轴各元素的一般生物学特性，重点关注分子相互作用以及各元素与SLE的潜在相关性。
仅能促进适度B细胞清除的药物贝利尤单抗取得了成功，而能促进深度B细胞清除的抗CD20单克隆抗体利妥昔单抗却失败了，本文对此提出了多种观点来解释这一明显的矛盾。文中介绍了贝利尤单抗治疗的实际和感知到的局限性，并讨论了靶向BAFF/APRIL轴特定元素的其他治疗药物的可能性。
