CD63 and autoimmune disease: The presence of large EVs is not limited to autoimmune diseases, but they have been documented in OA SF,4,5 and they also include cancer cell-derived EVs.6 To accommodate the MISEV guidelines for studies on EVs,29 these structures were shown to have intact lipid membranes and to stain with membrane tetraspanin CD63 and phalloidin that binds cytosolic actin5 (Fig. 1B), and they lacked staining of nuclei by NucBlue.