Background: A role for dendritic cells (DC) in the development of adult rheumatoid arthritis has been suggested. To date, this problem has been poorly explored in juvenile idiopathic arthritis (JIA). Objective: To analyse distribution and maturation status of blood DC (BDC) in JIA. Methods: Absolute BDC counts were assessed by the “single platform” method in peripheral blood (PB) of 47 untreated children with JIA and 32 healthy controls. Moreover, BDC were investigated in JIA synovial fluid (SF). When the panel of monoclonal antibodies against BDC antigens (BDCA) was used, three BDC subpopulations were determined: myeloid type 1 (mDC1; BDCA-1+/HLA-DR+/CD19−), myeloid type 2 (mDC2; BDCA-3+/HLA-DR+/CD14−) and plasmacytoid (pDC; BDCA-2+/HLA-DR+/CD123+). Results: A considerable deficiency of all subtypes of BDC was found in the PB of children with JIA. BDC counts in JIA SF were significantly higher than in PB both from children with JIA (p<0.001) and healthy children (p<0.001). SF BDC, especially mDC1 and mDC2 subtypes, had significantly higher expression of maturation markers (CD40, CD80, CD86 or CD83 antigens) than those from PB. A smaller number of PB BDC at diagnosis correlated significantly with poor response to treatment. Conclusions: A deficiency of BDC in PB is accompanied by enrichment of SF with those cells. Probably, circulating BDC migrate to joints where they undergo maturation and help to mediate and maintain the local immune response. Interestingly, the level of PD BDC deficiency seems to influence the outcome in children with JIA.

Background. Defining new prognostic biomarkers has become one of the most promising perspectives for the long-term care of patients with juvenile idiopathic arthritis (JIA). The new efficient indicators of disease activity and potential response to treatment are crucial in establishing new therapeutic plans in accordance with the “treat to target” strategy. One of the most studied proteins is called S100A12, which is an alarmin specific for granulocytes, considered as a marker of their activity. Materials and Methods. Study involved 80 patients diagnosed with JIA. Children with systemic subtype were not included in the study. In 53 cases, blood samples were obtained in two time points. Results from the study group were compared to 29 age- and sex-matched healthy individuals. Results. Serum S100A12 levels were higher in JIA than in healthy controls at the study baseline (11.67 ± 6.59 vs. 6.01 ± 2.33 ng/ml). There were no significant differences in S100A12 values between assessed subtypes of JIA. The highest concentrations were observed in patients within a disease flare. S100A12 levels were not dependent from using glucocorticosteroids. The studied protein appeared to be an efficient biomarker for JIA patients: 100% specificity as a diagnostic marker (cut-off level: 10.73 ng/ml) and 100% sensitivity as an indicator of exacerbations within a 3-month observation (cut-off level: 5.48 ng/ml). Conclusions. S100A12 may become an important factor influencing decisions on aggressiveness of JIA therapy. Further elaboration on the clinical algorithm is necessary for that protein to be included in everyday practice.

Background: Methotrexate is the most commonly used disease-modifying antirheumatic drug recommended in the treatment of juvenile idiopathic arthritis. It can be administered orally or subcutaneously, the latter method is associated with fewer side effects and higher drug bioavailability. Nevertheless, the pain associated with injection is a considerable drawback of this treatment option in the pediatric population. Currently, there are two single-use subcutaneous injection devices available: the prefilled syringe and the prefilled pen. This prospective, two-sequence crossover study aimed to compare ease of use, frequency of therapy side effects, injection-site pain and parent/patient preference of those methotrexate parenteral delivery systems. Methods: Twenty-three patients with juvenile idiopathic arthritis, already treated with subcutaneous methotrexate in the form of prefilled syringe in the period October 2018 – April 2019 completed a questionnaire evaluating their experience with this device. Subsequently, children received a one-month supply of pen autoinjector and completed the same questionnaire, regarding their experience with the new methotrexate delivery system. If the patient was not performing the injections himself the questionnaires were completed by the caregiver administrating MTX. The results obtained in both questionnaires were compared using the Wilcoxon matched-pairs signed-rank test. Results: 82,6% patients and their caregivers voted for the prefilled pen as their preferred method of subcutaneous methotrexate administration. Moreover, the injection with the prefilled pen was reported as less painful in comparison to the prefilled syringe (p < 0.01). Side effects of methotrexate were less pronounced after the prefilled pen treatment, this difference was most prominent regarding gastrointestinal adverse events associated with the injection (p < 0.01). Conclusion: Administration of methotrexate using the pen device is a promising way of subcutaneous methotrexate delivery in children with juvenile idiopathic arthritis, as the injection is less painful and associated with fewer side effects.

Efficacy and safety of tocilizumab (TCZ), an interleukin-6 receptor inhibitor, were demonstrated in juvenile idiopathic arthritis (JIA) with polyarticular course (pJIA) in the CHERISH trial. This observational, III phase study evaluated long-term treatment of TCZ in pJIA patients was conducted by members of the Pediatric Rheumatology International Trials Organization (PRINTO) from Poland and Russia. Forty-one patients, who had completed the CHERISH core study (104 weeks), were extensionally treated with TCZ (8 mg/kg, intravenous infusion every 4 weeks). Total treatment time was from 131 to 193 weeks. The long-term safety (the primary endpoint) and efficacy were evaluated. All patients achieved ACR70 response in the core study and continued to achieve at least ACR50 response up to week 24 of this study. The safety population comprised 46.41 patient-years (PY). Rates per 100 PY of adverse (AEs) and serious events (SAEs) were 181.0 and 6.46, respectively. Pharyngitis and respiratory tract infections were the most common AEs. Except one AE (severe neutropenia), all others were classified as mild (24.4%) or moderate (29.3%). The incidence of SAEs was low (7.3%). No new safety findings were observed. The safety profile of over 2.5-year treatment with TCZ is consistent with the pre-marketing CHERISH clinical trial. Presented data and continued efficacy response support the use of TCZ in pJIA. EUDRACT No: 2011-001607-12. https://clinicaltrials.gov/ct2/show/study/NCT01575769?term=ML27783

Angiogenesis is the complex process of creating new capillaries from preexisting blood vessels due to hypoxemia, injury or inflammation of the tissues. Numerous cytokines and cell mediators have been identified to induce and stimulate angiogenesis, but vascular endothelial growth factor (VEGF) is a key regulator. The role of proangiogenic factors in the pathogenesis of chronic arthritis is currently a subject of intensive investigations in adult patients with rheumatoid arthritis (RA) and, to a limited extent, in children with juvenile idiopathic arthritis (JIA). Recent studies has shown a significant correlation between proangiogenic marker concentrations and the severity of inflammation in either RA or JIA patients. The serum neovascularization markers correlate with the power Doppler ultrasound image of the inflamed joint and hypertrophic synovium, which may be connected with the disease activity. The aim of this paper is to describe the state of the art on the important role of angiogenesis in adult and childhood rheumatoid arthritis.