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Tofacitinib Modula a Resposta Imune in vitro de Células T CD4+ VZV – Específicas em Linfócitos de Pacientes com Artrite Reumatoide

Almanzar A, Kienle F, Schmalzing M, Maas A, Tony H-P, Prelog M. - Rheumatology (Oxford) 2019;58(11):2051–60

TOF significantly modulated the Th1 response to Varicella-zoster-virus (VZV). The poor VZV-specific cellular immune responses in patients with RA may be considered in recommendations regarding appropriate vaccination strategies for enhancing the VZV-specific Th1 response.

Previous studies have shown that treatment with JAKinibs increases HZ incidence compared with conventional DMARDs. This cross-sectional in vitro study aimed to investigate the effect of TOF on the VZV-specific T cell immune response. Peripheral blood mononuclear cells and serum samples were collected from 46 patients with RA, and 46 healthy donors, all of whom had a history of wild-type VZV infection during childhood.

Significantly lower levels of IgG-anti-VZV antibodies and proliferating VZV-specific CD4+ T cells were found in patients with RA compared with healthy donors, and there was dose-dependent inhibition of proliferation in both short- and long-term culture. TOF did not influence differentiation of naive into VZV-specific effector and memory CD4+ T cells, but it did reduce the activation of T cells. Extracellular IFNγ decreased with high concentrations of TOF, but this difference did not reach statistical significance; no difference in IFNγ production was found at low concentrations of TOF.

This in vitro study in lymphocytes derived from RA patients demonstrates for the first time that TOF reduces IFNγ production, and significantly decreases the proliferation, activation, and CXCR3 expression of VZV-specific CD4+ T cells in a dose-dependent manner. These findings may explain the diminished control of latent VZV infection by Th1 cells in RA patients treated with TOF.

Keywords: JAK, Tofacitinib, Clinical, Safety

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Upload date: November 2019

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