Treatment with Tofacitinib Inhibits Human Naive B Lymphocyte Development and Function in Vitro

Jens Thiel¹, Nils Venhoff², Raquel Lorenzetti³, Bettina Bannert¹, Reinhard Voll⁴, Diego Kyburz⁵ and Marta Rizzi¹, ¹Department of Internal Medicine, Clinic for Rheumatology and Clinical Immunology, Freiburg, Germany, ²Department of Internal Medicine, Clinic for Rheumatology and Clincal Immunology, Freiburg, Germany, ³Department of Internal Medicine, Clinic for Rheumatology and Clinical Immunology, 79106, Germany, ⁴Dpt. Rheumatology & Clinical Immunology and Centre for Chronic Immunodeficiency, University Hospital Freiburg, University Medical Center, University of Freiburg, Freiburg, Germany, ⁵Department of Biomedicine, Experimental Rheumatology, University of Basel, 4051 Basel, Switzerland

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: antibodies and tofacitinib, B cells

Session Information

Date: Monday, November 14, 2016

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy - Poster II

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.

Disclosure: J. Thiel, None; N. Venhoff, None; R. Lorenzetti, None; B. Bannert, None; R. Voll, None; D. Kyburz, None; M. Rizzi, None.

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 .

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