Cytokine profile present in peripheral blood from very early rheumatoid arthritis (VERA) patients and synovial fluid from established RA. A group of cytokines directly related with B cell activation, differentiation and survival was quantified in serum samples from untreated very early rheumatoid arthritis (VERA) patients with <6 weeks of disease duration when compared to healthy controls (A). In addition, serum and synovial fluid samples from established treated RA patients were also analyzed for comparison (A). Cytokines related with neutrophil and Th17 cells activation were also quantified in serum samples from VERA patients and healthy individuals (B). Furthermore, synovial fluid from established treated RA and osteoarthritis (OA) patients was analyzed for comparison (B). Statistical analysis of data was performed with GraphPad Prism (GraphPad Software, San Diego, CA, USA). Lines in graphs represent median values with interquartile range. Non-parametric Mann-Whitney test was used for comparisons between two independent groups. Differences were considered statistically significant for p < 0.05. Data represented in Figures 1A,B were adapted from previous published studies by our group (16–18), according to the terms of the Creative Commons license (http://creativecommons.org/licenses/by/4.0/). Figure 1C is an illustration representative of the cytokine profile present in peripheral blood from VERA patients and synovial fluid from established RA supported by previous published studies by our group (16–18). To sum up, RA patients have a cytokine profile in peripheral blood that favors B cells, neutrophils and Th17 cells activation since the first weeks of disease development. In a chronic phase of the disease, the cytokine pattern present locally in the joints supports the intervention of activated monocytes, neutrophils, T and B cells and plasma cell differentiation (C). ACPA, anti-citrullinated protein antibodies; APRIL, a proliferation-inducing ligand; BAFF, B cell activating factor; IL, interleukin; ns, non-significant; OA, osteoarthritis; RA, rheumatoid arthritis; RF, rheumatoid factor; Th17, T helper 17; VERA, very early rheumatoid arthritis.