Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: B cells are pivotal to the pathogenesis of many autoimmune diseases including rheumatoid arthritis (RA). Tofacitinib, a JAK inhibitor, is effective and safe in the treatment of RA. Tofacitinib interferes with signal transduction via cytokine receptors using the common γ-chain.Despite of extensive data on T lymphocytes, the impact of tofacitinib on B lymphocytes is poorly understood. In this study we assess the effect of tofacitinib on the differentiation of naive B-lymphocytes and their function.
Methods: Sorted human B cells from cord blood or buffy coat were stimulated in the presence of increasing doses of tofacitinib. B cell phenotypes were determined by flow cytometry. Immunoglobulin concentrations were measured by ELISA. The expression of B cell fate determining genes PRDM1, IRF4, XBP1, and AICDA was analyzed by quantitative RT-PCR.
Results: Tofacitinib treatment strongly impaired plasmablast development, immunoglobulin secretion and induction of PRDM1, IRF-4, and XBP-1 from naive B cells. Interestingly, class switch and AICDA induction from activated naive B cells was only slightly reduced. B cells purified from buffy coats, including naive and memory B cells, stimulated in the presence of tofacitinib, showed only a moderate reduction in plasmablast formation, immunoglobulin secretion and proliferation.
Conclusion: We demonstrated that tofacitinib has a direct impact on human naive B-lymphocytes, independently from its effect on T lymphocytes, by impairing their development into plasmablasts and immunoglobulin secretion. Tofacitinib predominantly affects naive B lymphocytes, while its effect on total peripheral B cells containing naive and memory B cells is less pronounced. Our data are of clinical importance as they suggest that vaccinations should be performed prior to tofacitinib treatment. Furthermore, impairement of B cell function by tofacitimib may directly contribute to its therapeutic effects. This fact has implications for the potential use of tofacitinib in B cell-mediated diseases.
To cite this abstract in AMA style:Thiel J, Venhoff N, Lorenzetti R, Bannert B, Voll R, Kyburz D, Rizzi M. Treatment with Tofacitinib Inhibits Human Naive B Lymphocyte Development and Function in Vitro [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/treatment-with-tofacitinib-inhibits-human-naive-b-lymphocyte-development-and-function-in-vitro/. Accessed September 17, 2019.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/treatment-with-tofacitinib-inhibits-human-naive-b-lymphocyte-development-and-function-in-vitro/