SAT0074 DAS-28 DISEASE ACTIVITY DEFINES THE TNFR1/2 CO-EXPRESSION PROFILE IN RHEUMATOID ARTHRITIS PATIENTS

Background: TNF-alpha act as main proinflamantory cytokine in rheumatoid arthritis (RA) immune processes. However, TNF-alpha activity and functions may be regulate not only by soluble receptors (which act as decoys) but also by number, density, and co-expression of its membrane-bound receptors type 1 and 2 (TNFR1 and TNFR2). Objectives: To analyze the TNFR1\2 co-expression profile in RA patient with different disease activity in comparison to healthy donors (HD). Methods: PBMC were analyzed from 46 HD and 64 patients with RA using flow cytometry. Patients were divided according to the DAS-28 index into groups with high (n=22, 34.4%), moderate (n=30, 46.9%) and low (n=12, 18.8%) disease activity. Co-expression of TNFR1/2 was evaluated as percentage of cell with different receptors. Number of receptors of each type per cell was counted using QuantiBrite PE beads (BD, USA). The following populations were analyzed: total monocyte pool; common pool of B lymphocytes; common pool of T lymphocytes; cytotoxic T cells (CD8+), T helper cells (CD4+), activated (CD25+) cells among CD8+ and CD4+, T memory (CD45R0+) and naive T cells (CD45RA+) among cytotoxic and T helper cells; T regulatory cells (CD4+CD25highCD127low); B1 cells (CD45+CD19+CD5+). Results: We found that analyzed cell populations differ significantly in the co-expression of type 1 and 2 receptors for TNFα both between each other and compared to healthy donors. The most pronounced differences between groups of patients in the expression profile were shown for B cells, T reg and memory cells (figure). The total proportion of cells with at least one type of receptors was significantly decreased as compared with HD (in the case of B cells, T-helper memory cells) or increased (in the case of naive cytotoxic T cells, naive T helper cells, monocytes, T regs). This indicator may reflect the overall sensitivity of the cells of the subpopulation to the effects of cytokine. This mechanism may reflect the ability of the cells to react on certain TNF-alpha concentration or anti-cytokine therapy. Conclusion: The profile of TNFR1\2 co-expression is changed in RA compared to heath. RA disease activity is associated with the changes in the amount and co-expression of type 1 and type 2 receptors for TNF-alpha on the surface of immunocompetent cells. Disclosure of Interests: None declared