Background Janus kinase inhibitors (JAKi) are a new therapeutic class approved for the treatment of chronic arthritis. JAKi suppress the activity of STAT tyrosine kinases, interfering with the signaling pathway which is critical for immune cell proliferation, survival and differentiation. Our group has demonstrated that early treatment with a JAKi, in animal models, abrogates disease and prevent bone damage. We hypothesize that JAK-STAT pathway is key to chronic arthritis onset and its early inhibition might have a major effect on disease control.

Objectives The main goal of this study is to characterize the JAK-STAT signaling pathway activation in untreated early arthritis patients.

Methods Peripheral blood mononuclear cells were isolated from blood samples collected from untreated early arthritis patients (<12 months of disease duration). Frequency, phenotype and STAT phosphorylation (by mean fluorescence intensity, MFI) levels were evaluated on T and B cells, monocytes and dendritic cells (DC) by flow cytometry. A group of age and sex-matched healthy individuals was included for comparison.

Results The frequency of total CD19+ B cells was similar between patients and controls, although patients presented a significantly decreased level of pre-switch memory B cells when compared to controls. No significant differences were observed in naïve, post-switch memory, double negative B cells, transitional B cells and plasmablasts. The frequency of total CD3+ T cells, CD14+ monocytes and DCs was similar, however patients had significantly decreased levels of plasmacytoid DCs. In addition, we found that STAT3 phosphorylation levels were significantly increased in B cells and DCs in early arthritis patients. The STAT1, STAT5 and STAT6 phosphorylation levels were similar in T and B cells, monocytes and DCs, when compared with the control group.

Conclusion Alterations in the frequencies of circulating memory B cell subsets and pDCs, but not in T cells and monocytes, are found in untreated early arthritis patients when compared to healthy controls. Changes in STAT3 phosphorylation MFI levels observed in B cells and DCs from early arthritis patients in comparison to controls support an early activation of JAK-STAT pathway in the initial phase of arthritis and a role of these cells in disease pathogenesis.

Acknowledgements We would like to thank the Flow Cytometry Facility of Instituto de Medicina Molecular João Lobo Antunes for their technical support and also Clinical Research Center of the Lisbon Academic Medical Center for their nurse support.

Disclosure of Interests Rui Lourenço Teixeira: None declared, Catarina Tomé: None declared, Ana Rita Faísca: None declared, Vasco C Romão: None declared, Joao Eurico Fonseca Grant/research support from: Abbvie., Isabel Alcobia: None declared, Rita A. Moura: None declared.