Mackay Fabienne, Groom Joanna R, Tangye Stuart G
The Autoimmunity Research Unit, The Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia.
Curr Opin Rheumatol. 2007 Sep;19(5):406-13. doi: 10.1097/BOR.0b013e328277ef4c.
This review provides an update on the specific, strong association between dysregulated production of the cytokine B-cell activation factor and Sjögren's syndrome, and offers new perspectives on potential pathogenic mechanisms.
Excess B-cell activation factor in mice triggers Sjögren's syndrome-like symptoms, and elevated serum B-cell activation factor in humans correlates with Sjögren's syndrome. B-cell activation factor is produced locally by activated monocytes, T cells and dendritic cells, and by epithelial cells and infiltrating B cells. Moreover, recent data in humans suggest that the innate immune system plays a role as an initiator of immune disorders in inflamed tissues.
Recent data have demonstrated the critical role of B-cell activation factor and B cells in the pathogenesis of Sjögren's syndrome, and its association with B lymphomas. Moreover, B-cell depleting treatments have confirmed the critical role of B cells in Sjögren's syndrome. Excess B-cell activation factor possibly corrupts B-cell tolerance and allows the emergence of self-reactive B cells that efficiently present antigen to T cells. In addition, B-cell activation factor may stimulate T-cell independent activation of B cells via Toll-like receptors; this recently identified mechanism could also play a separate, detrimental role in autoimmunity.
本综述提供了关于细胞因子B细胞活化因子产生失调与干燥综合征之间特定的、紧密关联的最新情况，并就潜在的致病机制提供了新的观点。
小鼠体内过量的B细胞活化因子会引发类似干燥综合征的症状，而人类血清中B细胞活化因子水平升高与干燥综合征相关。B细胞活化因子由活化的单核细胞、T细胞和树突状细胞以及上皮细胞和浸润的B细胞在局部产生。此外，近期人类研究数据表明，先天免疫系统在炎症组织的免疫紊乱起始过程中发挥作用。
近期数据已证明B细胞活化因子和B细胞在干燥综合征发病机制及其与B淋巴瘤关联中的关键作用。此外，B细胞清除疗法已证实B细胞在干燥综合征中的关键作用。过量的B细胞活化因子可能破坏B细胞耐受性，使自身反应性B细胞出现，这些细胞能有效地将抗原呈递给T细胞。此外，B细胞活化因子可能通过Toll样受体刺激B细胞的非T细胞依赖性活化；这一最近发现的机制在自身免疫中也可能发挥独立的有害作用。
