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AB0027 Expression density of receptors to TNF-ALPHA is associated with DAS-28 score in rheumatoid arthritis
  1. AA Alshevskaya1,
  2. J Lopatnikova1,
  3. N Shkaruba1,
  4. O Chumasova1,
  5. A Sizikov1,
  6. V Lukinov2,
  7. A Moskalev2,3,
  8. S Sennikov1
  1. 1Federal State Budgetary Scientific Institution “Research Institute of Fundamental and Clinical Immunology”
  2. 2EOL Labs Ltd
  3. 3Biostatistics and Clinical Trials Center, Novosibirsk, Russian Federation

Abstract

Background For a number of cytokines and growth factors density of receptors expression has been shown to be important in regulation of action intensity and variation. Although TNF-alpha is actively involved in the development and progression of chronic inflammation in rheumatoid arthritis (RA) role of membrane receptors and their regulatory function in RA remains unclear.

Objectives To assess associations of membrane-bound receptors expression and soluble receptors and cytokine content with disease activity score in patients with rheumatoid arthritis.

Methods To reveal linear relationships among integrated score DAS-28 and studied parameters of intact T-cells, B-cells and monocytes (evaluated by flow cytometry) and parameters of mediators soluble content (evaluated by ELISA) building of multiple linear regression model (MLRM) with a standard assessment of the regression coefficients by least squares method were used. To determine receptor number on the cells QuantibritePE Beads (BD) were used.

Results For the group of patients with acute stage of RA MLRMs with best statistical quality characteristics revealed that for lymphocytes both TNFR1 and TNFR2 number had significant associations with DAS-28; for monocytes only number of TNFR2 was significant. Lower DAS-28 index is associated with higher number of TNFR2 per cell and lower number of TNFR1.

Comparison of models with different combinations of studied TNFR-parameters revealed that percentages of cells expressing receptors for TNFα validated not more than 20% of DAS-28 variation, while the number of receptors indicators on cells validated 40–50% of DAS-28 variation. Full MLRM with all 15 studied parameters validated about 70% of DAS-28 variation.

For the group of patients with acute stage of RA MLRMs with best statistical quality characteristics revealed that for lymphocytes both TNFR1 and TNFR2 number had significant associations with DAS-28; for monocytes only number of TNFR2 was significant. Lower DAS-28 index is associated with higher number of TNFR2 per cell and lower number of TNFR1. Comparison of models with different combinations of studied TNFR-parameters revealed that percentages of cells expressing receptors for TNFα validated not more than 20% of DAS-28 variation, while the number of receptors indicators on cells validated 40–50% of DAS-28 variation. Full MLRM with all 15 studied parameters validated about 70% of DAS-28 variation.

Conclusions Number of receptors to TNF-alpha is more associated with RA activity score as compared with soluble receptors or cytokine. Number of receptors type 1 and type 2 to TNF-alpha per cell have opposite influence on disease activity score. Our findings indicate the involvement of receptors expression density changes in the pathological process in RA.

Disclosure of Interest None declared

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