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

doi:10.3390/ijms21010288

Co-Expression Profile of TNF Membrane-Bound Receptors Type 1 and 2 in Rheumatoid Arthritis on Immunocompetent Cells Subsets

Int J Mol Sci. 2019 Dec 31;21(1):288. doi: 10.3390/ijms21010288.

Affiliations

¹ Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology (RIFCI). 630099 Novosibirsk, Russia.
² Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation. 119435 Moscow, Russia.
³ Biostatistics and Clinical Trials Center, 630090 Novosibirsk, Russia.
⁴ Novosibirsk State University. 630090 Novosibirsk, Russia.

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. Co-expression 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.

Keywords: TNF; co-expression; cytokine receptors; disease activity; rheumatoid arthritis.

MeSH terms

Adult
Aged
Arthritis, Rheumatoid / immunology*
Arthritis, Rheumatoid / pathology
CD8-Positive T-Lymphocytes / immunology*
CD8-Positive T-Lymphocytes / pathology
Female
Gene Expression Regulation / immunology*
Humans
Immunologic Memory*
Male
Middle Aged
Receptors, Tumor Necrosis Factor, Type I / immunology*
Receptors, Tumor Necrosis Factor, Type II / immunology*
T-Lymphocytes, Regulatory / immunology*
T-Lymphocytes, Regulatory / pathology

Substances

Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
TNFRSF1A protein, human
TNFRSF1B protein, human