Tolusso Barbara, De Santis Maria, Bosello Silvia, Gremese Elisa, Gobessi Stefania, Cuoghi Ilaria, Totaro Michele C, Bigotti Giulio, Rumi Carlo, Efremov Dimitar G, Ferraccioli Gianfranco
Division of Rheumatology, School of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Clin Immunol. 2009 Apr;131(1):98-108. doi: 10.1016/j.clim.2008.11.011. Epub 2009 Jan 12.
B cells have acquired an important role in the pathogenesis of rheumatoid arthritis (RA) since B cell depletion allowed to rescue patients poorly responders to TNFalpha blockers. This study focused on the involvement of ZAP-70 as a bio-marker of B cells immune activation in RA. ZAP-70 expression in synovial fluid (SF) B cells obtained from RA patients was increased compared to SF B cells of osteoarthritis (OA) patients. Moreover we found that ZAP-70 positive/CD38 positive and ZAP-70 positive/CD5 positive B cells were enriched in SF. The analysis of B cell apoptosis in vitro showed that the percentage of ZAP-70 negative B cells spontaneously undergoing apoptosis was significantly higher than ZAP-70 positive B cells. The ZAP-70 positive B cell ratio (SF/peripheral blood (PB)) showed a positive correlation with SF autoantibody levels and with local levels of BAFF and IL6. ZAP-70 positive B cells seem to define a subset characterized by increased survival and high relationship with local inflammation and autoimmunity.
自从发现B细胞清除疗法能使对肿瘤坏死因子α阻滞剂反应不佳的患者病情得到缓解以来，B细胞在类风湿性关节炎（RA）发病机制中的重要作用已得到确认。本研究聚焦于ZAP-70作为RA中B细胞免疫激活生物标志物的作用。与骨关节炎（OA）患者的滑膜液（SF）B细胞相比，RA患者的SF B细胞中ZAP-70表达增加。此外，我们发现SF中ZAP-70阳性/CD38阳性和ZAP-70阳性/CD5阳性B细胞增多。体外B细胞凋亡分析表明，自发发生凋亡的ZAP-70阴性B细胞百分比显著高于ZAP-70阳性B细胞。ZAP-70阳性B细胞比例（SF/外周血（PB））与SF自身抗体水平以及BAFF和IL6的局部水平呈正相关。ZAP-70阳性B细胞似乎定义了一个以存活率增加以及与局部炎症和自身免疫高度相关为特征的亚群。
