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SAT0008 Drug therapy enhances tolerogenic properties of dendritic cells in patients with rheumatoid arthritis
  1. Y Kurochkina1,
  2. M Tikhonova2,
  3. T Tyrinova2,
  4. O Leplina2,
  5. A Sizikov1,
  6. A Sulutian1,
  7. L Konenkova1,
  8. O Chumasova1,
  9. A Ostanin2,
  10. E Chernykh2
  1. 1Department of Rheumatology
  2. 2Laboratory of Cellular Immunotherapy, Federal State Budgetary Scientific Institution Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation

Abstract

Background Dendritic cells (DCs) are known to contribute to the pathogenesis of rheumatoid arthritis (RA) through presentation of cartilage glycoprotein, production of proinflammatory cytokines and activation of Th1/Th17 responses. Along with stimulating activity, DCs may exhibit suppressive functions via capacity to induce T cell apoptosis/anergy and to generate regulatory T cells. Since these DCs have potential to control autoreactive T-lymphocytes, the enhancing of tolerogenic properties of DCs seems to be a new important strategy in treatment of RA. The experimental research in animals and human in vitro studies revealed the capacity of anti-rheumatic drugs to inhibit stimulating activity and to enhance tolerogenic functions of DCs. However, data concerning the in vivo influences of drug therapies on DC functions in RA patients are not available.

Objectives The aim of our study is to investigate, whether drug therapies influence the properties of monocyte-derived DCs generated in the presence of IFNα (IFN-DCs) in RA patients, and if the effect of disease-modifying anti-rheumatic drugs differ from that of biological/pulse steroid therapy.

Methods Thirty nine patients with RA with high and moderate activity of disease were recruited in this study. All patients fullfield ACR/EULAR criteria (2010). Nineteen patients received methotrexate, leflunomide, sulfasalazine or their combination (RA1). Twenty patients were at pulse therapy (methylprednisolone 500mg No. 3) or biological drugs (adalimumab or rituximab) (RA 2). All studies were performed after receiving informed consent. DCs were generated from blood monocytes culturing for 5 days with GM-CSF and IFN-α in the absence and presence dexamethasone, applied on third day. LPS as maturation stimuli was added on fourth day. The expression of CD14, CD83, CD 86, B7H1, HLA-DR, TLR-2 on the surface of DCs was measured by flow cytometry. The functions of DCs were evaluated by measuring cytokine production and DC allostimulatory activity in mixed lymphocyte culture.

Results Both DC-RA1 and DC-RA2 where shown to display impaired maturation evidenced by elevated expression of CD14 and decreased number of mature (CD14-CD83+) DCs. Wherein, DCs-RA2 demonstrated several additional differences, including increased number of intermediate CD14+CD83+ cells (compared with donors DCs), higher expression of inhibitory molecule B7-H1 (PD-1L) (compare with donors DCs and DCs-RA1) and tendency to lower expression of CD86 and higher expression of TLR-2. Besides, DCs-RA2 produced higher concentrations of IL-6 and had 2-fold lower allostimulatory activity then DCs-RA1. These differences together with phenotypic changes suggested more pronounced tolerogenic properties of DCs-RA2. Despite the revealed DC differences in RA1 and RA2 patients both types of DCs preserved in vitro sensitivity to dexamethasone, that suppressed the production of TNF-α and reduced allostimulatory activity.

Conclusions The data obtained indicate that, IFN-DCs from RA patients at drug treatments are characterized by tolerogenic properties, which are more pronounced in patients with biological or pulse steroid therapy.

Disclosure of Interest None declared

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