FURIN is a proprotein convertase enzyme that inhibits the pro-inflammatory function of T cells and myeloid cells. Previously, elevated FURIN expression levels have been reported in immune-mediated diseases, such as primary Sjögren's syndrome. Here, we investigated the levels of FURIN in peripheral blood (PB) and synovial fluid (SF) leukocytes from patients with rheumatoid arthritis (RA). Methods FURIN mRNA expression in PB and SF cells was determined by qRT-PCR and FURIN plasma levels were measured using ELISA. Associations between FURIN levels and demographic and clinical characteristics of the patients were determined. Results FURIN levels were significantly elevated in PB and SF mononuclear cells, T cells and monocytes from RA patients when compared to healthy controls. High FURIN levels were significantly associated with the prevailing prednisolone treatment, higher prednisolone doses as well as increased CRP levels and Health Assessment Questionnaire (HAQ) values. Conclusion FURIN is significantly upregulated in RA PB and SF leukocytes, suggesting that FURIN may have a role in the pathogenesis of RA. In addition, our results suggest that elevated FURIN expression is associated with the indicators of more severe RA.

The data on effects of tofacitinib on soluble proteins in patients with rheumatoid arthritis (RA) is currently very limited. We analysed how tofacitinib treatment and thus inhibition of the Janus kinase – signal transducer and activation on transcription pathway affects the in vivo levels of inflammation-related plasma proteins in RA patients. In this study, sixteen patients with active RA [28-joint Disease Activity Score (DAS28) >3.2] despite treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) started tofacitinib treatment 5mg twice daily. Levels of 92 inflammation-related plasma proteins were determined by proximity extension assay at baseline and at three months. Tofacitinib treatment for three months, in csDMARD background, decreased mean DAS28 from 4.4 to 2.6 (p<0.001). Marked (>20%) and statistically significant (p<0.05) changes were found in the levels of 21 proteins, 18 of which decreased and three increased. Of these proteins 17 are directly involved in inflammatory responses or in the cellular response to cytokines. Highest (>50%) decrease was observed for interleukin-6 (IL-6), C-X-C motif chemokine ligand 1, matrix metalloproteinase-1 and AXIN1. Higher baseline level of IL-6, and lower levels of C-C motif chemokine 11 and Delta and Notch-like epidermal growth factor-related receptor were associated with DAS28 improvement. Our results indicate that tofacitinib downregulates several proinflammatory plasma proteins which may contribute to the clinical efficacy of tofacitinib. In addition, soluble biomarkers may predict the treatment response to tofacitinib.

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