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AB0071 Relation Between Serum and Synovial Fluid Levels of IL-1-ALPHA, TNF-ALPHA, IL-6, IFN-Gamma and SIL-6R and Clinical, Immunological and Genetic Factors in Rheumatoid Arthritis Patients
  1. Z. Kolarov1,
  2. I. Altankova2,
  3. M. Baleva3,
  4. F. Martinova4,
  5. S. Monov1,
  6. R. Shumnalieva1
  1. 1Clinic of rheumatology
  2. 2Clinic of Immunology
  3. 3Laboratory of clinical immunology
  4. 4Laboratory of hemotransfusion and immunogenetics, Medical University - Sofia, Sofia, Bulgaria

Abstract

Background Rheumatoid arthritis (RA) is an autoimmune rheumatic disease with unknown etiology. It is believed that the disease pathogenesis results from the interaction between environmental factors and genetic and epigenetic factors which leads to immune dysregulation. The autoimmune process responsible for the disease onset and progression raises the interest for investigating immune and genetic factors in the serum and synovial fluid of RA patients. This could show individual characteristics of the pathogenic process and possible correlation with the clinical phenotype and treatment respond.

Objectives The objectives of our study were to analyze the serum and synovial fluid (SF) cytokine levels in RA patients and to compare them with known genetic risk factor for RA and clinical and immunological data in regard to their use as biomarkers for disease activity and treatment decisions.

Methods 42 RA patients according to the 1987 ACR criteria were included in the study. Serum and SF samples were used for measuring the levels of IL-1α, TNF-α, IL-6, sIL-6R by ELISA kit (Immunotech, FRA) and IFN-γ by ELISA kit (Genzyme, USA). The blood samples were used for detecting the HLA-DR4 phenotype. The results were analyzed in regard to the clinical picture including radiological stage, the laboratory data for disease activity, immunological markers and possible targeted treatment.

Results SF samples showed higher levels of IL-6 and lower levels of sIL-6R compared to serum levels. Serum and SF TNF-α levels correlated with serum and SF sIL-6R levels. Patients with high disease activity score showed higher serum TNF-α, IL-6 and higher SF sIL-6R level than patients with low disease activity according to RA Disease Activity Score 28 (DAS28). Serum TNF-α levels were higher in patients with active disease as defined by DAS28 score, in IgM rheumatoid factor positive patients and in patients with higher scores for disease progression based on the results from the ultrasound and radiologic examination. IL-1α and IFN-γ were detected in serum and SF samples of few patients with no significant correlations to any clinical setting or disease activity. There was no association between HLA-DR4 positivity and serum and SF levels of the pro-inflammatory cytokines (IL-1α, TNF-α, IL-6, sIL-6R) in this subset of RA patients.

Conclusions Levels of pro-inflammatory cytokines in the serum and SF of RA patients correlate with disease activity and progression. In the era of biological drugs such studies will eventually show if cytokine levels could be used in the clinical practice in the process of making treatment decisions with personalizing the biological therapy.

References

  1. Moura RA, Cascão R, Perpétuo et al. Cytokine profile in serum and synovial fluid of patients with established rheumatoid arthritis, Ann. Rheum. Dis, 2010; 69: A51

  2. Takeuchi T, Miyasaka N, Tatsuki Y et al. Baseline tumour necrosis factor alpha levels predict the necessity for dose escalation of infliximab therapy with rheumatoid arthritis, Ann. Rheum. Dis., 2011; 70(7): 1208-1215.

  3. Wang J, Platt A, Upmanyu R et al. IL-6 pathway-driven investigation of response to IL-6 receptor inhibition in rheumatoid arthritis, BMJ Open, 2013; 3: e003199.

Disclosure of Interest None declared

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