SAT0027 Co-expression of receptors to tnfΑ among naÏve t-cells and memory t-cells is altered in rheumatoid arthritis and the changes correlate with disease activity
Authors: A.A. Alshevskaya, J. Lopatnikova, O. Chumasova, N. Shkaruba, A. Sizikov, V. Gladkikh, S. Sennikov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Changing the ratio of TNFα receptors of different types can lead to shift in the balance between pro-apoptotic and proliferative signalling pathways which is crucial for rheumatoid arthritis (RA) inflammatory processes. <h3>Objectives</h3> To study the level of expression of type 1 and 2 receptors for TNFα (TNFR1/TNFR2) on individual subpopulations of peripheral blood actively involved in immunopathological processes in RA <h3>Methods</h3> The study included 20 healthy donors aged 18–60 years (11 men (55%)) and 36 RA patients with high (n=14), medium (n=15) and low (n=7) disease activity at the age of 22–77 years (31 women (86, 1%)). Co-expression and number of type 1 and 2 receptors for TNFα were calculated for monocytes, B-cells, T-cells, as well as among: cytotoxic T-cells (CD8+), T-helper cells (CD4+), activated CD8 +cells, activated CD4 +cells, memory T-cells (CD45R0+) and naive T-cells (CD45RA+) from cytotoxic and T-helper cells, and T-regulatory cells (CD4 +CD25highCD127low) by flow cytometry analysis (BD FacsVerse, USA). <h3>Results</h3> Seven indicators of receptor expression were revealed, which differed in patients with RA with high disease activity in comparison with HD, and didn't differ between HD and patients with low disease activity. These were 4 indicators on the number of receptors on cells and 3 cell percentages with specific combinations of expressed. The association between disease severity and activity indexes (DAS-28 index, disease duration, X-ray stage, activity stage, RF level, ASCP and C-RB, systemic manifestations and erosive arthritis) and parameters of TNFα receptor expression on immunocompetent cell subpopulations were studied. The following associations were revealed: RF level positively correlated with the percentage of double-positive TNFR1 +TNFR2+cells among naive and memory T-cells for both T-helpers and cytotoxic T-cells (r levels from 0.62 to 0.68 with p&lt;0.05); the level of C-reactive protein positively correlated with the percentage of cells carrying only receptor type 1 among all the T-lymphocyte subpopulations studied (r levels from 0.73 to 0.9 with p&lt;0.05); the presence of systemic manifestations is negatively correlated with the number of receptors of both types 1 and 2 on naive T-helper and cytotoxic cells (r levels from −0.63 to −0.74 with p&lt;0.05). <h3>Conclusions</h3> The active inflammatory process in rheumatoid arthritis with DAS28 &gt;5.1 is accompanied by a change in the ratio of cells with different variants of co-expression of receptors to TNFα among populations actively involved in the pathological process (naïve T-cells and memory T-cells among T-helpers and cytotoxic T-cells). The selected parameters will be used to construct and verify the predictive models of response to therapy of different subclasses <h3>Disclosure of Interest</h3> None declared