Background Rheumatoid arthritis (RA) is a systemic connective tissue disease and characterized by inflammation of synovium of multiple joints, however, its pathogenesis is still unclear (1). Physiologically, microparticle (MP) is categorized as a membrane microvesicle which contains various humoral factors such as cytokines or growth factors and 0.1–1 μm in size (2). And MPs can distribute systemically through circulation. MP is released from almost all cell types and induced by stimulation, stress or apoptosis (3). Thus, we hypothesized that MPs derived from various cells can distribute to the lesion of RA and be associated with systemic disease process of RA.
Objectives To clarify the source of MPs in circulation of RA and elucidate their role in the pathogenesis and the possibility for application as a novel disease marker.
Methods Twenty patients with RA and 13 healthy controls were involved. Using gradient centrifugation, platelet-rich plasma was isolated from whole blood and applied to flow cytometry. MP is defined as a vesicle less than 1 mm in diameter and Megamix® was used to set a gating condition to detect microparticles (4). Sources of MP (MP subsets) were identified by the expression of cell-specific markers using flow cytometry with fluorescence-conjugated antibodies as follows; platelets MP: CD41+CD31+ MP, endothelial cell MP: CD41-CD31+ MP, immune cell MP: CD45+CD41- MP, MP derived other cells: CD41-CD31-CD45- MP. Correlation between clinical information and proportion of MP subsets was also analyzed. Comparisons between two groups were examined by Mann-Whitney U-test with Bonferroni correction. Significant difference was defined as corrected p value (Pc) <0.05.
Results Mean age of 20 patients with RA was 56±14 years, 95% was female, disease duration was 8.5±8.0 years, and DAS28-ESR was 2.0±1.1. Methotrexate was administered to 75% and average dose was 8.0±2.4 mg/week. Platelet-derived MP covered the largest proportion in all groups. Interestingly, proportion of immune-cell-derived MP was higher (Pc<0.006) in patients with RA compared to controls. Proportion of immune-cell-derived MP was positively correlated with inflammatory markers such as CRP and composite disease markers such as DAS28-ESR. Furthermore, when stratified by monocyte fraction and non-monocyte fraction based on CD14 expression, proportion of monocyte-derived MP showed higher (Pc<0.01) in patients with RA compared to controls, but non-monocytes MP did not, and that of monocyte-derived MPs was also correlated with disease markers for activity of RA.
Conclusions Proportion of circulating immune-cell-derived MPs, especially monocyte-derived MPs, increased in RA and correlate with disease activity. These results suggest that monocyte-derived MPs can be measured as a novel biomarker and involved in the disease process of RA.
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Disclosure of Interest None declared