To investigate whether IgM-RF, as detected in plasma of RF+RA patients by ELISA, could also be detected in fraction 5 of the SEC isolated pEVs, IgM-RF ELISA was performed and in 46% (13 out of 28 RF+RA patients) IgM-RF was detectable (Figure 4A) while no IgM-RF was found in SEC eluent fraction 5 of RF−RA patients (data not shown). The gene discussed is CD40LG; the disease is rheumatoid arthritis.