BackgroundEarly diagnosis of rheumatoid arthritis (RA) is crucial to providing effective therapy and often hampered by unspecific clinical manifestations. Elevated levels of extracellular circulating DNA (cirDNA) in patients with autoimmune disease were found to be associated with etiopathogenesis. To our knowledge, this is the first study to investigate the putative diagnostic use of cirDNA in RA and its association with disease activity.MethodsBlood samples were taken from 63 healthy subjects (HS) and 74 patients with RA. cirDNA was extracted from plasma and cell surface-bound cirDNA fractions (csbDNA). cirDNA concentration was measured by quantitative real-time polymerase chain reaction. Rheumatoid factor was analyzed by immunonephelometry, whereas C-reactive protein and anticitrullinated protein/peptide antibodies (ACPA) were detected by enzyme-linked immunosorbent assay.ResultsPlasma cirDNA was significantly elevated in patients with RA compared with HS (12.0 versus 8.4 ng/ml, p < 0.01). In contrast, nuclear csbDNA (n-csbDNA) was significantly decreased (24.0 versus 50.8 ng/ml, p < 0.01), whereas mitochondrial csbDNA (m-csbDNA) was elevated (1.44 × 106 copies/ml versus 0.58 × 106 copies/ml, p < 0.05) in RA. The combination of csbDNA (mitochondrial + nuclear) with ACPA reveals the best positive/negative likelihood ratios (LRs) for the discrimination RA from HS (LR+ 61.00, LR− 0.03) in contrast to ACPA (LR+ 9.00, LR− 0.19) or csbDNA (LR+ 8.00, LR− 0.18) alone.ConclusionsNuclear and mitochondrial cirDNA levels in plasma and on the surface of blood cells are modulated in RA. Combination of cirDNA values with ACPA can improve the serological diagnosis of RA.Electronic supplementary materialThe online version of this article (doi:10.1186/s13075-017-1295-z) contains supplementary material, which is available to authorized users.

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IL-1β is involved in the induction and maintenance of chronic inflammation in rheumatoid arthritis (RA). Its activity is regulated and induced by soluble and membrane-bound receptors, respectively. The effectiveness of the cytokine depends not only on the percentage of receptor-positive cells in an immunocompetent subset but also on the density of receptor expression. The objective of this study was to investigate the expression of IL-1β membrane-bound receptors (IL-1R1 and IL-1R2) in terms of the percentage of receptor-positive cells and the number of receptors per cell in different subsets of immune cells in RA patients before and after a course of basic (excluding anticytokine) therapy and in healthy individuals. The resulting data indicate differences in the expression of IL-1β receptors among T cells, B cells, and monocytes in healthy volunteers and in rheumatoid arthritis patients. The importance of determining both the relative percentage of cells expressing receptors to immunomodulatory cytokines and the number of membrane-bound receptors per cell is highlighted by evidence of unidirectional or multidirectional changing of these parameters according to cell subset and health status.

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