Background:Previous studies of co-expression profile of receptors to tumor necrosis factor alpha (TNF) in rheumatoid arthritis (RA) have revealed a number of indicators associated with diseases activity with 93% sensitivity and 90% specificity. However, the ratio of receptors to cytokines remains poorly understood. However, the question of therapy effect and its effectiveness in various alteration of cytokine receptors balance remains under investigated.Objectives:To evaluate the dynamics of co-expression and quantitative expression of type 1 and 2 receptors for TNF in the subpopulations of CD3+CD8+ cells associated with changes in disease severity before and after effective basic therapy.Methods:Subanalysis of patients with high disease activity level successfully treated with methotrexate and oral glucocorticoids (n = 9) was performed. As a control group, we used data from 43 healthy donors, comparable by sex and age distribution. Subpopulations of cytotoxic T cells were studied, which were included in the final diagnostic models for differentiating different degrees of severity of RA: naive T cells and memory T cells. The dynamics of changes in the indicators of receptors number and proportion of cells expressing the corresponding receptor were compared.Results:For naïve cytotoxic T cells, the main revealed feature was the relative stability of the number of expressed receptors (both TNFR1 and TNFR2), regardless of the therapy, while this number did not significantly differ from healthy ones for TNFR1 and was significantly lower for TNFR2 (p <0.05 for all three fractions). At the same time, in terms of cell percentage, on the contrary, the therapy led to a change in total proportion of TNFR1 + cells closer to healthy donors indicators, and the proportion of TNFR2 + cells in the opposite direction.For cytotoxic T memory cells, it was demonstrated that after successful treatment a significant increase in the number of type 1 receptors was observed, with a decrease in TNFR1+ cells proportion, while these indicators were close to the values of healthy donors. At the same time, healthy donors were characterized by a significantly higher expression of type 2 receptors in terms of cell density of receptors. It is noteworthy that with successful therapy, a slight increase in the number of TNFR2 was observed with a sharp decrease in the proportion of TNFR2+ cells (p = 0.043).Conclusion:The balance of TNF receptor expression on cells actively involved in immunopathological processes affects both the density distribution of receptors on cells and co-expression in a subpopulation. Effective treatment of RA leads to equalization of the expression profile either by the percentage of cells or by the number of receptors, approaching the indicators of healthy donors, but not simultaneously.Disclosure of Interests:None declared
Susceptibility to Polyomavirus-Induced Tumors in Inbred Mice: Role of Innate Immune Responses
