Department of Rheumatology, CHRU la Cavale Blanche, Brest, France.
Immunotherapy. 2013 Jun;5(6):639-46. doi: 10.2217/imt.13.49.
Primary Sjögren's syndrome is a systemic autoimmune disease characterized by progressive exocrine gland destruction, resulting clinically in eyes and mouth dryness. To date, no treatment has been proven effective to modify the course of this slow-evolving disease. B cells are now considered to play a central role in the pathogenesis of primary Sjögren's syndrome because their functions are not restrained to antibody production. Thus, several B-cell targeting therapies are under clinical investigation. Rituximab, a monoclonal antibody directed to CD20 and leading to transient blood B-cell depletion, has shown partial improvements in subjective and objective sicca symptoms in small studies. However, the results of two large controlled trials are awaited before considering its use in large populations of patients. Several other therapeutic strategies are being studied, targeting other B-cell surface proteins (epratuzumab and anti-CD22) or major cytokines of B-cell homeostasis (e.g., BAFF, IL-6 and lymphotoxin-β). Although great hope is generated by the trials of these specific therapies, another challenge for clinical researchers is the development of reliable tools to assess the activity of Sjögren's syndrome and its response to treatment.
原发性干燥综合征是一种系统性自身免疫性疾病，其特征为进行性外分泌腺破坏，临床上表现为眼干和口干。迄今为止，尚无有效的方法可改变这种缓慢进展性疾病的病程。目前认为 B 细胞在原发性干燥综合征的发病机制中起核心作用，因为其功能不仅仅局限于产生抗体。因此，多种针对 B 细胞的治疗方法正在进行临床试验。利妥昔单抗是一种针对 CD20 的单克隆抗体，可导致 B 细胞一过性耗竭，在一些小型研究中显示对主观和客观干燥症状有一定改善。然而，在考虑将其用于大量患者之前，还需要等待两项大型对照试验的结果。目前还在研究其他一些治疗策略，包括针对其他 B 细胞表面蛋白（依帕珠单抗和抗 CD22）或 B 细胞稳态的主要细胞因子（如 BAFF、IL-6 和淋巴毒素-β）。虽然这些特定治疗方法的临床试验带来了很大的希望，但临床研究人员面临的另一个挑战是开发可靠的工具来评估干燥综合征的活动度及其对治疗的反应。
