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AB0159 Tnf membrane-bound and soluble receptors in health and in rheumatoid arthritis
  1. A. A. Alshevskaya1,
  2. J. A. Lopatnikova1,
  3. F. F. Vasiliev1,
  4. S. V. Sennikov1,
  5. N. Shkaruba1,
  6. O. Chumasova1,
  7. A. Sizikov1
  1. 1Sb Rams, Institute For Clinical Immunology, Novosibirsk, Russian Federation

Abstract

Background TNFα plays a critical role at all stages of the immunopathogenesis in rheumatoid arthritis (RA) [1]. Its soluble receptors potently regulate the cytokine activity in vivo, but the effects of mediator interaction with the target cells largelydepend not only on the percentage of receptors expressing cells in a subset [2], but also on the absolute number of membrane-bound receptors themselves.

Objectives To investigatethe expression of TNFα membrane-bound receptors: the percentage of cellswith these receptors, and the number of molecules expressed on cells of different subpopulations of immune cells, and to evaluate serum concentrations of soluble TNFα and its receptors (sTNFR1 and sTNFR2) in patients with rheumatoid arthritis and in healthy donors.

Methods The objects of the study are peripheral blood mononuclear cells (PBMC) of healthy donors and RA patients. To determine PBMC phenotype antibodies anti-hCD3-APC, anti-hCD19 PECy7, anti-hCD14 FITC (eBioscience), as well as anti-hTNFRI/II-PE (R & D Systems) were used. The mediator production averages were determined using ELISA kits: sTNFRI, sTNFRII (RayBiotech, Inc., USA) and alpha-TNF (ZAO “Vector-Best”, Russia). To determine receptor number on the cells Quantibrite PE Beads (BD) were used.

Results Among the studied subpopulations (T-, B-lymphocytes and monocytes) the largest percentage of TNFR1+ cells was estimated forthe monocytes CD14 +, and besidesthe percentage in healthy donors was significantly higher than inRA patients. But the greatest number of membrane-bound receptors was found in RA patients in acute stage, with significant decrease after clinical improvements to lower than in healthy donors level. CD3+ T cells demonstrated the highest percentage of TNFR2+ cells with the lowest absolute number of membrane-bound receptors among the all studied groups, and thehealthy donors had significantly higher characteristicsas compared with the RA patients.

Conclusions The identified differences in the TNFR1 expression indicated active involvement of high-expressing subset of T-lymphocytes in the RA inflammation and the differences in the TNFR2 expression can be explained by the active shedding inT-lymphocytes and consequently increasing the level of sTNFR2 in RA, which was the pathogenic marker of rheumatoid inflammation.

Thus, it was shown the different involvement of T-, B-lymphocytes and monocytes in the TNF-mediated processes at different stages of the pathogenetic process and the importance of evaluating the absolute number of TNF receptors for diagnosis and prognosis of RA.

  1. Furst, D. E., Development of TNF inhibitor therapies for the treatment of rheumatoid arthritis // Clin Exp Rheumatol. – 2010. – N. 28(3 Suppl 59). – P. 5-12.

  2. Chen, B, Tong, Z, Ye, Q, Nakamura, S, Costabel, U, Guzman, J. Expression of tumour necrosis factor receptors by bronchoalveolar cells in hypersensitivity pneumonitis // Eur Respir J. – 2005. – N. 25(6). – P. 1039-1043.

Acknowledgements Work is supported by grant of FTP “Scientific and Scientific-Pedagogical Personnel of the Innovative Russia in 2009-2013” (GC No 02.740.11.0707).

Disclosure of Interest None Declared

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