AB0100 LONGER DISEASE DURATION OF RHEUMATOID ARTHRITIS IS ASSOCIATED WITH TNF RECEPTORS REDISTRIBUTION ON IMMUNOCOMPETENT CELLS AND CHANGES IN CELL SENSITIVITY TO CYTOKINE
| Autor: | A. Alshevskaya, J. Zhukova, J. Lopatnikova, O. Chumasova, N. Shkaruba, A. Sizikov, S. Sennikov |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Annals of the Rheumatic Diseases. 81:1181.1-1181 |
| ISSN: | 1468-2060 0003-4967 |
| Popis: | BackgroundLonger duration of rheumatoid arthritis (RA) is associated not only with higher disease severity, but also with lower treatment efficacy including anticytokine therapy. One of key mechanisms implementing this is changing in expression of cytokines and their receptors actively involved in the pathological process, such as tumor necrosis factor (TNF).ObjectivesThe aim of the study was to study the redistribution of TNF receptors in patients with different duration of RA and depending on the severity of the disease.MethodsSubanalysis of RA patients with disease duration less than 10 years (Early RA group, n=34) and more than 10 years (Late RA group, n=30) was performed. Late RA patients had DAS-28 activity comparable with Early RA group (4.98 vs 4.69, p=0.68), but had higher radiological stage, higher levels of inflammatory markers, and more often received biologics and had systemic features. As a control group, data from 43 comparable healthy donors were used. Co-expression profile of TNF receptors type 1 and 2 (TNFR1/2) were assessed in main mononuclear subsets: T cells, B cells, monocytes, Tregs, T helpers, cytotoxic T cells. Dynamics of percentage of cells with different co-expression combination was estimated as well as receptors expression density per cell.ResultsThe redistribution of receptors on 12 subpopulations of immune cells was studied. Two types of cell responses were associated with disease duration increase. The first trend was presented by monocytes, regulatory T cells and general pool of cytotoxic T cells and consisted in significant decrease in TNFR2 expression density with simultaneously increase of double-positive TNFR1+TNFR2+ cells percentage and decrease of TNFR1-TNFR2+ cells percentage with no changes in proportion of cells without receptors, as compared with health and with disease progression. The second type of response was presented by B cells, T cells, T helper naïve cells and activated T cells and represented a significant increase in TNFR1 expression density and increase of double-positive cells proportion compared to health without influence of disease duration and tendency to decrease in proportion of cells without receptors over time.ConclusionTwo trends in the response of immunocompetent cells to changes in the level of TNF that occur during chronic inflammation in RA were established. These two trends demonstrate the reactive and adaptive mechanisms of immune cells actively involved in pathological process and are of significant interest for the possibilities of modulating cell sensitivity to the proapoptotic and proinflammatory effects of cytokine and for futher development of targeted RA therapy.AcknowledgementsThe study was supported by a grant from the Russian Science Foundation (project No. 20-75-10051)Disclosure of InterestsNone declared |
| Databáze: | OpenAIRE |
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