Activation of Syk in Peripheral Blood B Cells in Patients With Rheumatoid Arthritis: A Potential Target for Abatacept Therapy. Issue 1 (January 2015) - Iwata, Shigeru
Abstract Objective B cells play a pivotal role in the pathogenesis of autoimmune diseases. Although Syk functions as a key molecule in B cell receptor signaling, the pathologic role of Syk in B cells in rheumatoid arthritis (RA) remains unclear. The purpose of this study was to assess the relevance of activation of Syk in B cells to the pathologic development of RA and to the responsiveness of RA patients to treatment with biologics. Methods Healthy subjects (n = 36) and patients with moderate or severe RA disease activity (n = 70) were studied. The phosphorylation of Syk (pSyk) in peripheral blood B cells was measured by flow cytometry, and its correlation with clinical characteristics and changes after administration of biologic agents was evaluated. Results Levels of pSyk in peripheral blood B cells were preferentially higher in patients with RA compared to healthy subjects. Patients with significantly higher pSyk levels were strongly positive for anti–citrullinated protein antibodies (ACPAs). High pSyk levels were not correlated with the severity of disease activity. Treatment with abatacept, but not tumor necrosis factor inhibitors, significantly reduced the levels of pSyk in RA peripheral blood B cells. Abatacept also significantly reduced the proportion of follicular helper T (Tfh) cells. Conclusion Levels of pSyk in peripheral blood B cells were significantly elevated in patients with RA, and these patients also exhibited strong positivity for ACPAs. These data suggest that abatacept seems to inhibit the phosphorylation of Syk in B cells, as well as the development of Tfh cells, thus highlighting the relevance of B cell–T cell interactions as a potential target of abatacept therapy in RA.