Investigation of TNF receptor coexpression parameters as potential biomarkers of effective hospital therapy with rituximab in patients with rheumatoid arthritis
Abstract
Introduction. One of the main mechanisms regulating the biological action of tumor necrosis factor (TNF) as a key proinflammatory cytokine initiating pathological changes in rheumatoid arthritis (RA) is a change in the coexpression and expression density of specific receptors (TNFR1 and TNFR2). The search and testing of biomarkers associated with the regulation of cytokine activity is necessary to predict response to therapy and develop personalized strategies for managing patients with RA.
The aim of the study was to identify the parameters of expression and coexpression of TNFR1/TNFR2 associated with an insufficient effect after a course of hospital therapy with rituximab in terms of maintaining a long-term low activity of RA.
Material and methods. The study of expression and coexpression parameters of type 1 and type 2 receptors to TNF on immunocompetent cells of patients with RA was carried out by multicolor flow cytometry. Logistic regression analysis was used to identify potential biomarkers in patients with relapse after effective inpatient therapy.
Results. Among the 144 studied parameters of TNFR1/TNFR2 expression, 13 indicators were identified for 4 subpopulations of immunocompetent cells, which can be used as potential predictive biomarkers of long-term maintenance of low disease activity after rituximab therapy. It has been shown that combinations of expression parameters make it possible to calculate the level of response to therapy with greater prognostic significance compared to standard anamnestic, clinical and laboratory parameters. The final model included the percentage of TNFR2+ cells among monocytes [OR 0.861 (0.727 : 0.952), p = 0.023] and the number of TNFR1 on T cells [OR 1.636 (95 % CI 1.174 : 3.262), p = 0.038] with a determination coefficient of 0.52.
Conclusion. Changes in the coexpression profiles of TNF receptors on immunocompetent cells from patients with rheumatoid arthritis are associated with the level of response to therapy and the stability of remission.
Keywords:TNF; TNFR1; TNFR2; receptor expression density; receptor expression level; rheumatoid arthritis
For citation: Alshevskaya A.A., Lopatnikova Yu.A., Zhukova Yu.V., Kireev F.D., Gladkikh V.S., Shkaruba N.S., Chumasova O.A., Sizikov A.E., Sennikov S.V. Investigation of TNF receptor coexpression parameters as potential biomarkers of effective hospital therapy with rituximab in patients with rheumatoid arthritis. 2023; 44 (4): 429–42. DOI: https://doi.org/10.33029/1816-2134-2023-44-4-429-442 (in Russian)
Funding. The work was performed within a state task «The study of expression indicators of cytokine receptors and their ligands in the formation of functional properties and the type of response of cell populations of various genesis in normal and pathological conditions», registration number in USAIS RDTCW 122011800353-4.
Conflict of interests. The authors declare no conflict of interests.
Authors’ contribution. The concept and design of the study – Alshevskaya A.A., Lopatnikova Yu.A., Sennikov S.V.; collection and processing of material – Kireev F.D., Shkaruba N.S., Chumasova O.A., Sizikov A.E.; statistical data processing – Alshevskaya A.A., Zhukova Yu.V., Lopatnikova Yu.A., Gladkikh V.S.; writing the text – Alshevskaya A.A., Zhukova Yu.V., Lopatnikova Yu.A., Gladkikh V.S.; editing – Sennikov S.V., approval of the final version of the article – Sennikov S.V.; responsibility for the integrity of all parts of the article – Alshevskaya A.A.
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