Internal Medicine Department, Hospital Virgen de la Luz, Calle de la Hermandad de Donantes de Sangre, Cuenca 16002, Spain.
Rheum Dis Clin North Am. 2010 May;36(2):325-43. doi: 10.1016/j.rdc.2010.02.003.
Initially suggested by the presence of rheumatoid factor autoantibodies, multiple pathogenic roles for B cells (both antibody-mediated and antibody-independent) in rheumatoid arthritis (RA) now are supported by a growing body of experimental observations and human studies. The pathogenic significance of B cells in this disease also has been established conclusively by the proven benefit of Rituximab-induced B cell depletion in RA patients refractory to tumor necrosis factor (TNF) blockade. This article reviews the rationale for the use of B cell-targeting therapies in RA and discusses the caveats and limitations of indiscriminate B cell depletion as currently applied, ncluding incomplete depletion of pathogenic B cells and elimination of protective B cells. Finally, it presents alternative therapeutic strategies that exploit current knowledge of B cell activation, survival, and differentiation to provide more selective B cell and plasma cell targeting.
最初是由类风湿因子自身抗体的存在提示，B 细胞（抗体介导和非抗体依赖的）在类风湿关节炎（RA）中的多种致病作用，现在得到了越来越多的实验观察和人类研究的支持。B 细胞在这种疾病中的致病意义也已被证明，即利妥昔单抗诱导的 B 细胞耗竭对肿瘤坏死因子（TNF）阻断治疗抵抗的 RA 患者具有显著疗效。本文综述了在 RA 中使用 B 细胞靶向治疗的原理，并讨论了目前应用的非选择性 B 细胞耗竭的注意事项和局限性，包括对致病性 B 细胞的不完全耗竭和对保护性 B 细胞的消除。最后，提出了利用当前对 B 细胞激活、存活和分化的认识的替代治疗策略，以提供更具选择性的 B 细胞和浆细胞靶向治疗。
