Background/Purpose:: Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that mainly affects synovial joints. Most research on RA has focused on cytokines as main effectors in disease progression however, cell-cell communication involves a much broader scope of responses. Cells can release additionally extracellular vesicles (EVs) and an important role of these EVs has been postulated as important communicators between resident and inflammatory cells [1]. B-cells also release EVs that contain the B-cell receptor on their surface which is an immunoglobulin that binds and presents antigens to T-cells [2]. The presence of IgM-RF in seropositive RA patients clearly points to a role of B-cells and plasma cells in the pathogenesis of this disease. In this study we investigate the presence of RF-IgM on circulating EVs and the relation to the severity of RA.

Methods: EVs were isolated from platelet-free plasma of 41 RA patients and 24 healthy controls (HC) by size exclusion chromatography. We quantified the particle and protein concentration, using NanoSight particle tracking analysis and micro-BCA. Tender (TJC) and swollen joints (SJC) were assessed by physicians and the global patient visual analogue score (VAS) was determined by the patient. IgM-RF, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels were determined by standard laboratory blood tests in our hospital. Disease activity score (DAS28) was calculated.

Results: RA and HC pEVs were not different in particle size, protein content and particle concentration (115nm, 49fg, 3.5×10¹⁰ and 108nm, 45fg, 3.8×10¹⁰, respectively). Between seronegative (RA-) and seropositive (RA+) patients, particle size, protein content per particle and amount of particles of pEVs were not statistically different (116nm, 39fg, 5.410¹⁰ and 114nm, 58fg, 1.8×10¹⁰, respectively). In plasma of 28 out of 41 RA patients IgM-RF was detectable, and in 13 out of these 28 RA+ IgM-RF was also detected on their isolated pEVs (RF⁺pEVs). In RA- patients we did not find any RF present on pEVs. When comparing disease parameters we found no differences between RA+ and RA- patients, except for increased ESR levels in RA+ patients. However, RA+ patients with RF⁺pEVs showed significant higher levels of CRP and ESR and also VAS and DAS28 were significant increased compared to RA+ patients without RF⁺pEVs.

Conclusion: This study shows for the first time the presence of IgM-RF on pEVs in a subset of RA+ patients with a more severe disease. The presence of RF⁺pEVs may point to a higher B-cell involvement in the disease process in these patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/rheumatoid-arthritis-patients-with-circulating-extracellular-vesicles-positive-for-igm-rheumatoid-factor-have-higher-disease-activity/