Synovial‐fluid‐derived microparticles express vimentin and GRP78 in their surface and exhibit an in vitro stimulatory effect on fibroblast‐like synoviocytes in rheumatoid arthritis

Abstract Objectives To investigate the hypothesis that microparticles (MP) may be a source of autoantigens and drive disease progression in rheumatoid arthritis (RA) synovium. Methods Synovial fluid (SF) was collected from the knee joints of 41 disease‐modifying anti‐rheumatic drug‐naive RA patients and 30 osteoarthritis (OA) patients. Samples were stained with either anti‐vimentin‐AlexaFluor‐488 or anti‐glucose‐regulated protein‐78‐Dylight‐488 (GRP78) and Annexin‐V‐allophycocyanin for flow cytometry analysis. RA and OA fibroblast‐like synoviocytes (FLS) were co‐cultured with respective SF‐derived MP in vitro for 24 h. Supernatant and cell‐free SF was assayed for pro‐inflammatory analytes by multiplex assays. Results Elevated percentages of AnnexinV + Vimentin + MP (median 0.8, interquartile range [IQR] 1.30) and AnnexinV + GRP78 + MP (median 0.3, IQR 0.28) were present in RA compared with OA patients. We observed that CXCL6 and CCL8 were secreted in excess by RA‐FLS stimulated with RA‐SF‐MP but not by stimulation with MP‐free RA‐SF. Conclusions Microparticles express vimentin and GRP78 on their surface and stimulate synoviocytes to produce inflammatory molecules, thus sustaining local inflammation in the synovium in RA.