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Background Dendritic cells (DCs) are known to contribute to the pathogenesis of rheumatoid arthritis (RA) through thepresentation of cartilage glycoprotein, production ofproinflammatory 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, utilization of tolerogenicDCs seems to be a promising immunotherapeutic toolto treat RA. Objectives The aim of our study is to evaluate the safety and tolerability of a single intra-articular injection(into the knee joint) of autologous monocyte-derived dendritic cells generated in the presence of IFN-α/GM-CSFand tolerized with Dexamethasone inRApatients. Methods DCs were generated by culturing blood monocytes for 5 days with GM-CSF and IFN-α in the presence dexamethasone, applied on third day. Azoximer bromides maturation stimuli was added on fourth day. Twelve RA patients with moderate and high disease activity and ultrasound-defined kneesynovitis were recruited in this study. All patients fullfield ACR/EULAR criteria (2010) and received methotrexate, leflunomide, sulfasalazine or their combination. The patients received intra-articular injections of1*106, 3*106, 5*106,8*106,10*106DCs in knee joints. Safety was assessed by evaluation of adverse events (AE). Acceptability was assessed by questionnaire. DAS28 and HAQ were used for assessment of treatment efficiency. This trial registered on clinicaltrials.gov (ID:NCT03337165). Results DCs injections were safe and well tolerated. No one participants showed worsening of symptoms in targeting knee, fever, elevation of blood pressure or other AE within 7 days after injection. All patients, evaluated at 6 months follow-up showed a good EULAR response (improvement of DAS28-ESR >1.2). The median DAS28-ESR decreased from 5.1to 3.1 (p=0.03). The median pain VAS score decreased from 52 (41-70) mm to 42 (15-55) mm; p=0.04. In addition, we detected median HAQ improvement (from 1.45 to1.0; p=0.04).The effect of treatment had been continued for 6 month and after that we indicated escape of effect. Conclusion The data obtained suggest that single intra-articular injection of autologous tolerogenic dendritic cells is safe, well tolerated, and have a potential not long term efficiency and requires the repeating of procedure. Disclosure of Interests None declared |
