Previously, CD16+ monocytes found in the SF of RA patients have been associated with elevated levels of proinflammatory cytokines and joint destruction17,49, and RA patients have shown a negative correlation between intermediate monocyte frequency and disease activity scores; however, in our study we did not find this association (Figure S2 and data not shown), instead, we found that alterations in intermediate monocytes and EVs, along with the elevated serum concentrations of IL-6, TNF-α, and IL-1β, were closely related in seropositive patients. Here, IL6 is linked to rheumatoid arthritis.