Background:The balance of TNFα receptors expression on cells which are actively involved in immunopathological processes affects both the density of distribution of receptors on cells and co-expression in subsets. Previously it was shown that basic effective RA therapy with methotrexate and glucocorticoids leads to equalization of the expression profile either in the percentage of cells or in the number of receptors, approaching those of healthy donors, but not simultaneously. However, questions about the relationship between the effectiveness of biological therapy and receptors co-expression remain unknown.Objectives:To assess the differences in co-expression and quantitative expression of TNF receptors type 1 and 2 in subsets of cells associated with the severity of the disease, depending on the response to rituximab therapy.Methods:Subanalysis of patients with high disease activity level successfully treated with rituximab (alone or in combination treatment scheme) during hospitalization was performed (n = 14). The first group included 6 patients who retained low disease activity during 1 month follow-up (RA, stabilization). The second group consisted of 8 patients who had exacerbation during follow-up period. As a control group, we used data from 43 comparable healthy donors. Subsets of T regulatory cells and monocytes were studied. A comparison was made among the indicators of receptors number and proportion of cells expressing the corresponding receptor.Results:For T regulatory cells, the key differences for patients who did not retain low disease activity were significantly higher number of TNF type 1 and type 2 receptors on double-positive cells with a lower percentage of these cells compared to stable patients. At the same time, higher differences between proportions of double-positive cells in comparison with control values of healthy donors were associated with higher probability of maintaining in remission.For monocytes, the key differences in stable patients were the very high quantitative expression of type 1 receptors on double-positive cells, with a lower percentage of these cells compared to patients with exacerbation. At the same time, lower differences between proportions of double-positive cells in comparison with control values of healthy donors were associated with higher probability of maintaining in remission.Conclusion:Obtained data confirm the previously proposed hypothesis about the essential role of balance in quantitative expression of TNF receptors type 1 and 2 on double-positive cells to determine the intensity and type of cell response to the mediator and its association with the level of disease activity and response to therapy.Acknowledgements:This study is supported by grant of the President of the Russian Federation for state support of young Russian PhD scientists №МК-2433.2020.4Disclosure of Interests:None declared
Variability of disease activity in patients with hereditary angioedema type 1/2: longitudinal data from the Icatibant Outcome Survey