Co-expression profile of TNF membrane-bound receptors type 1 and 2 in rheumatoid arthritis on immunocompetent cells subsets

Alina Alshevskaya, Julia Lopatnikova, Julia Zhukova, Oksana Chumasova, Nadezhda Shkaruba, Aleksey Sizikov, Irina Evsegneeva, Victor Gladkikh, Aleksander Karaulov, Sergey V. Sennikov

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Abstract

Introduction: Tumor necrosis factor (TNFα) is an important proinflammatory cytokine in rheumatoid arthritis (RA) immune processes. However, TNFα activity and functions may be regulated by soluble receptors, which act as decoys, and by number, density, and co-expression of its membrane-bound receptors type 1 and 2 (TNFR1 and TNFR2). The aim of this study was to reveal associations between TNFR1/2 co-expression profile parameters and RA disease activity indicators. Methods: PBMC were analyzed from 46 healthy donors and 64 patients with RA using flow cytometry. Patients were divided according to the disease activity score (DAS) 28 index into groups with high (n = 22, 34.4%), moderate (n = 30, 46.9%), and low (n = 12, 18.8%) disease activity. Coexpression of TNFR1 and TNFR2 was studied by evaluating the percentage of cells, with different receptors, and by counting the number of receptors of each type per cell, using QuantiBritePE beads. Associations between disease severity and activity indicators and parameters of TNFα receptor expression in subpopulations of immune cells were studied. Results: T cell subsets from RA patients were characterized by co-expression of TNFR1 and TNFR2, and were found to differ significantly compared with healthy donors. Memory cells both among T helper cells and cytotoxic T cells demonstrated the most significant differences in TNFR-expression profile. Multivariable logistic regression revealed model to identified RA patients from healthy individual based on the TNFR1/2 co-expression parameters. Conclusion: The profile of TNFR1\2 co-expression differs in RA comparing with health. Proportion of TNFR1+TNFR2-cells increased significantly among memory T helper cells and activated cytotoxic T cells, and decreased significantly among naïve cytotoxic T cells and T regulatory cells as compared with health. The parameters of TNFR1\2 co-expression in RA are associated with clinical and laboratory indicators of disease activity.

Original languageEnglish
Article number288
Number of pages13
JournalInternational Journal of Molecular Sciences
Volume21
Issue number1
DOIs
Publication statusPublished - 1 Jan 2020

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Keywords

  • Co-expression
  • Cytokine receptors
  • Disease activity
  • Rheumatoid arthritis
  • TNF
  • co-expression
  • disease activity
  • cytokine receptors
  • rheumatoid arthritis
  • EXPRESSION

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