Date: Monday, November 6, 2017
Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Cardiovascular disease (CVD) constitutes a relevant cause of morbidity and mortality in Rheumatoid Arthritis (RA) patients. Rituximab (RTX) has been proved to be effective in the treatment of RA, indicating that B-cells play a crucial role in the pathogenesis of the disease, not only through the production of autoantibodies. Moreover, B-cells seem to be important in the development of CVD. However, the effect of RTX in the context of CVD in RA patients has not been fully elucidated yet.Therefore, the aims of this study were to evaluate the mechanism of action of RTX on immune and endothelial cells and to investigate the effect of B-cells depletion in the context of CVD in RA patients.
Methods: The analysis includes 10 RA patients with moderate-high disease activity based on Disease Activity Score using 28 joints. To evaluate the influence of B-cells depletion on the inflammatory profile of T-cells, purified lymphocytes from 6 RA patients were treated with RTX (1µg/ml) for 24 hours. B-cells depletion was assessed by flow cytometry and the changes in the inflammatory profile were analyzed by RT-PCR. Following, to identify changes in the activity of crucial mediators in the production of pro-inflammatory cytokines, a western blot was performed on extracted proteins from purified lymphocytes of the 6 RA patients treated with RTX. In a second set of experiments, supernatant from cultured lymphocytes of 6 RA patients, in the presence or in the absence of RTX, was added to cultured endothelial cells (HUVECs) and monocytes isolated from Healthy Donors (HDs) and the response was analyzed by RT-PCR. Finally, serum from 4 RA patients at baseline and after 3 months of therapy with RTX, was added to HUVECs and monocytes isolated from HDs and the response was analyzed by RT-PCR.
Results: In parallel to a significant depletion of B-cells, we observed a downregulation of the pro-inflammatory profile of T-lymphocytes, as shown by a significant drop of IL1, IL6, IL17, IFNγ, and TNFα genes expression levels. We also found a decrease in the phosphorylation and protein expression of STAT-3 and p38 in lymphocytes treated with RTX, compared to non-treated T-cells. HUVECs and monocytes cultured with supernatant of RA-lymphocytes treated with RTX, showed a decrease in the expression levels of various pro-thrombotic factors (i.e. TF, IL8, and VEGF) as well as cell-adhesion molecules (i.e. V-CAM, I-CAM and e-Selectin). Both HUVECs and monocytes, treated with serum of RA patients after 3 months of therapy with RTX, showed a reduced expression of genes related to their pro-thrombotic and pro-inflammatory profile.
Conclusion: Overall, RTX showed a beneficial effect in the context of CVD in RA patients, through the modulation of the inflammatory and pro-thrombotic profile of distinct leukocytes subtypes and vascular endothelial cells. Supported by CTS-794, ISCIII (PI15/01333; RIER RD16/0012/0015)
To cite this abstract in AMA style:Cecchi I, Perez-Sanchez C, Ruiz-Limon P, Arias de la Rosa I, Abalos-Aguilera MC, Jiménez-Gómez Y, Ortega-Castro R, Collantes-Estévez E, Escudero-Contreras A, Radin M, Barbarroja N, Roccatello D, Sciascia S, Lopez-Pedrera C. The Effects of Rituximab and B-Cells Depletion on the Inflammatory and Pro-Thrombotic Profile of Leucocytes of Rheumatoid Arthritis Patients and on the Vascular Endothelium [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/the-effects-of-rituximab-and-b-cells-depletion-on-the-inflammatory-and-pro-thrombotic-profile-of-leucocytes-of-rheumatoid-arthritis-patients-and-on-the-vascular-endothelium/. Accessed October 24, 2020.
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