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AB0056 Expression of Receptors to IL-1 on Peripheral Blood Immunocompetent Cells in Rheumatoid Arthritis
  1. A.A. Alshevskaya1,
  2. J. Lopatnikova1,
  3. N. Shkaruba2,
  4. F. Vasiliev1,3,
  5. O. Chumasova2,
  6. A. Sizikov2,
  7. S. Sennikov1
  1. 1Laboratory of Molecular Immunology
  2. 2Rheumatology Department, Federal State Budgetary Scientific Institution “Research Institute of Fundamental and Clinical Immunology”, Novosibirsk
  3. 3Laboratory of Genome Medicine, North-Eastern Federal University, Yakutsk, Russian Federation

Abstract

Background IL-1 is involved in the induction and maintenance of chronic inflammation in rheumatoid arthritis (RA). [1]. Its effects can be exhibited only after binding to specific membrane-bound IL-1R1, while IL-1R2 act as decoy. Therefore, the balance between different types of soluble and membrane-bound receptors will determine whether a cell responds to IL-1 or not and variability in intracellular effects.

Objectives To investigate the expression of IL-1β receptors in RA patients before and after a course of basic (excluding anti-cytokine) therapy.

Methods PBMCs were isolated from blood samples collected from RA patient during the acute stage (n=40) and after effective basic therapy (n=21) involved either rituximab or methylprednisolone. The control group contained 150 healthy individuals (HI). To determine IL-1Rs expression density by flow cytometry antibodies anti-hIL-1R1/2 PE (R&D Systems, USA), anti-hCD3 APC, anti-hCD19 PE-Cy7, anti-hCD14 FITC (eBioscience, USA) and QuantiBRITE PE calibration beads (BD, USA) were used. Serum protein levels were evaluated using ELISA kits for sIL-1R1/2 (RayBiotech, USA), IL-1β and raIL-1 (JSC Vector-Best, Novosibirsk, Russia).

Results As the changes in density of receptor expression on the cell surface can be a key mechanism in regulation of cytokines biological properties [2], the comprehensive assessment and comparison of the levels of soluble factors and expression of membrane-bound receptors were performed on cells which are actively involved in the systemic and local inflammatory response. Table summarizes the data on differences obtained for RA patients as compared with HI, as well as the differences between the phases of the disease.

It was found that B cells and monocytes showed oppositely directed changes in percentage of IL-1R1-positive cells and the number of receptors on these cells in RA patients compared with HI. Also it was found that both the percentage and receptor expression density in HI significantly differs for IL-1R1 and IL-1R2 in each subpopulation studied. RA patients do not exhibit these differences, regardless of the phase of the disease.

Conclusions The resulting data indicate differences in the expression of IL-1β receptors among T cells, B cells and monocytes in RA patients. The importance of determining both the relative percentage of cells expressing receptors to immunomodulatory cytokines and the number of membrane-bound receptors per cell is highlighted by evidence of unidirectional or multidirectional changing of these parameters according to cell subset and health status.

References

  1. Dinarello CA, van der Meer JW. Treating inflammation by blocking interleukin-1 in humans. Semin Immunol. 2013 Dec 15;25(6):469-84. doi: 10.1016/j.smim.2013.10.008.

  2. Booy S, van Eijck CH, Dogan F, van Koetsveld PM, Hofland LJ. Influence of type-I Interferon receptor expression level on the response to type-I Interferons in human pancreatic cancer cells. J Cell Mol Med. 2014;18(3):492-502.

Disclosure of Interest None declared

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