Nucleic acid aptamers capable of affine and specific binding to their molecular targets have now established themselves as a very promising alternative to monoclonal antibodies for diagnostic and therapeutic applications. Although the main focus in aptamers’ research and development for biomedicine is made on cardiovascular, infectious, and malignant diseases, the use of aptamers as therapeutic or diagnostic tools in the context of rheumatic diseases is no less important. In this review, we consider the main features of aptamers that make them valuable molecular tools for rheumatologists, and summarize the studies on the selection and application of aptamers for protein biomarkers associated with rheumatic diseases. We discuss the progress in the development of aptamer-based diagnostic assays and targeted therapeutics for rheumatic disorders, future prospects in the field, and issues that have yet to be addressed.

Background:Dendritic cells (DCs) are known to contribute to the pathogenesis of rheumatoid arthritis (RA) through the 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, utilization of tolerogenic DCs 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-CSF and tolerized with Dexamethasone in RA patients.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 bromide as maturation stimuli was added on fourth day. Ten RA patients with moderate and high disease activity and ultrasound-defined knee synovitis 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 of 1*106, 3*106, 5*106,8*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. After one month the median pain VAS score decreased from 45 (40–65) mm to 40 (15–40) mm; p=0.03. Ultrasound and clinical examination did not detect synovitis. At 3 month no patients demonstrated recurrence of synovitis and median DAS28-ESR improved from baseline 5.1 to 4.4 (p=0.008; n=10). Five patients, evaluated at 6 months follow-up showed a good EULAR response (improvement of DAS28-ESR >1.2). The median DAS28-ESR in this group decreased from 5.1to 3.3 (p=0.04).In addition, we detected median HAQ improvement (from 1.45 to1.0; p=0.04).Conclusions:The data obtained suggest that single intra-articular injection of autologous tolerogenic dendritic cells is safe, well tolerated, and according to preliminary data have a potential efficiency. However, the final conclusion should be done after the completion of the trial.Disclosure of Interest:None declared

Spondyloarthritis (SpA) encompasses a group of chronic inflammatory rheumatic diseases with a predilection for the spinal and sacroiliac joints, which include axial spondyloarthritis, psoriatic arthritis, reactive arthritis, arthritis associated with chronic inflammatory bowel disease, and undifferentiated spondyloarthritis. The prevalence of SpA in the population varies from 0.5 to 2%, most commonly affecting young people. Spondyloarthritis pathogenesis is related to the hyperproduction of proinflammatory cytokines (TNFα, IL-17А, IL-23, etc.). IL-17A plays a key role in the pathogenesis of spondyloarthritis (inflammation maintenance, syndesmophites formation and radiographic progression, enthesites and anterior uveitis development, etc.). Targeted anti-IL17 therapies have established themselves as the most efficient therapies in SpA treatment. The present review summarizes literature data on the role of the IL-17 family in the pathogenesis of SpA and analyzes existing therapeutic strategies for IL-17 suppression with monoclonal antibodies and Janus kinase inhibitors. We also consider alternative targeted strategies, such as the use of other small-molecule inhibitors, therapeutic nucleic acids, or affibodies. We discuss advantages and pitfalls of these approaches and the future prospects of each method.