Coca Andreea, Sanz Ignacio
Division of Allergy, Immunology and Rheumatology, University of Rochester, Rochester, New York 14642, USA.
Curr Opin Rheumatol. 2009 Sep;21(5):483-8. doi: 10.1097/BOR.0b013e32832efe55.
The critical role of B cells in the pathogenesis of systemic lupus erythematosus and Sjogren's syndrome has provided a strong rationale to specifically target B cells. This review summarizes recent advances in the field of B cell depletion in systemic lupus erythematosus and Sjögren's syndrome.
Reports of successful B cell depletion therapy in refractory SLE have continued to surface over the last year. The accumulation of positive results therefore stands in stark contrast to the recent reports that two phase III randomized placebo controlled trials employing B cell depletion with rituximab in nonlupus and lupus nephritis (Explorer and Lunar, respectively) did not achieve. Multiple reasons, including trial design, limitations of outcome instruments and sort follow-up have been invoked to explain these disconcerting results. In the representative studies addressing B cell depletion in lupus in the last year, complete and partial remission in lupus nephritis has been achieved in 60-89% of cases. Improvements in the British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were associated with decrease in anti-dsDNA and increase in complement levels. B cell depletion seemed quite efficacious also in pediatric SLE. While more definitive studies are still lacking for primary Sjogren's syndrome, incidental reports indicating potential efficacy have also been recently published.
Despite the disappointing results of Explorer and Lunar trials, other evidence continues to be published in support of the notion that B cell depletion could be useful for patients with refractory disease, including lupus nephritis, and antibody-mediated cytopenias, possibly in combination with other immunosuppressant medication.
B细胞在系统性红斑狼疮和干燥综合征发病机制中的关键作用为特异性靶向B细胞提供了有力依据。本综述总结了系统性红斑狼疮和干燥综合征领域中B细胞清除方面的最新进展。
去年，难治性系统性红斑狼疮患者成功接受B细胞清除疗法的报告不断涌现。因此，这些积极结果的积累与最近的报告形成了鲜明对比，即两项分别在非狼疮性肾炎和狼疮性肾炎中使用利妥昔单抗进行B细胞清除的III期随机安慰剂对照试验（分别为Explorer和Lunar试验）未取得成功。人们提出了多种原因来解释这些令人不安的结果，包括试验设计、结局指标的局限性以及随访时间短等。在去年针对狼疮患者B细胞清除的代表性研究中，60%至89%的狼疮性肾炎病例实现了完全或部分缓解。不列颠群岛狼疮评估组（BILAG）和系统性红斑狼疮疾病活动指数（SLEDAI）评分的改善与抗双链DNA水平降低和补体水平升高相关。B细胞清除在儿童系统性红斑狼疮中似乎也相当有效。虽然原发性干燥综合征仍缺乏更确切的研究，但最近也有一些偶然报告表明其可能具有疗效。
尽管Explorer和Lunar试验结果令人失望，但仍有其他证据支持B细胞清除对难治性疾病患者（包括狼疮性肾炎和抗体介导的血细胞减少症患者）可能有用的观点，可能与其他免疫抑制药物联合使用。
