Synovial angiogenesis is considered to be an important early step in the pathogenesis of juvenile idiopathic arthritis (JIA). In this study we assessed levels of angiogenic markers in serum or synovial fluid and their possible relevance to disease activity or degree of ultrasound signs of synovial inflammation and angiogenesis in early JIA. The concentration of vascular endothelial growth factor (VEGF), its soluble receptors 1 and 2 (sVEGF-R1, sVEGF-R2), and angiopoietins 1 and 2 (ANG-1, ANG-2) were evaluated in 43 JIA patients and 23 healthy controls. Synovial angiogenesis was assessed by means of Power-Doppler Ultrasonography (PDUS), according to the fourth-grade vascularity scale. VEGF and its receptors' (sVEGF-R1, sVEGF-R2) serum levels were significantly higher in JIA patients (p = 0.002). We found large variation in serum ANG-1 and ANG-2 levels. The PDUS imaging identified increased synovial microvascular blood flow in 15 (35.7%) examined JIA children. Intensity of joint vascularization correlated with higher serum VEGF and its levels was lowest in grade 0 and highest in grade 3 (p < 0.007 and p < 0.001, resp.). In conclusion, the high correlation between synovial microvascular blood flow, serum angiogenic proteins, and symptoms of synovitis may indicate its important role in pathogenesis of JIA.

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ObjectivesConnective tissue diseases (CTD) are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA). Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient's clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS), it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD.Material and methodsData from 24 patients with CTD treated with tumor necrosis factor-α-blockers (etanercept, adalimumab, golimumab) and an interleukin-6 receptor blocker (tocilizumab) were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy.ResultsPatient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1%) during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day.ConclusionsIn the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS daily doses.

BackgroundTumor necrosis factor α (TNFα) inhibitors in juvenile idiopathic arthritis (JIA) decrease synoviocyte proliferation and block a cascade of secondary mediators which play a part in the recruitment of inflammatory cells. By directly affecting endothelial cells and by inhibiting the production of proangiogenetic factors it suppress angiogenesis and reduces vascularization of inflamed joints.ObjectivesTo compare the neovascularization process by investigating serum angiogenesis markers (VEGF, sVEGF-R1, sVEGF-R2, ANG-1, ANG-2) in children with JIA receiving no treatment (new-diagnosed) and treated with TNFα inhibitors.MethodsForty three patients with new-diagnosed active JIA and eleven JIA patients treated with TNFα inhibitors (etanercept or adalimumab) plus methotrexate were studied. Serum levels of vascular markers were measured in each patient serum sample with a standard quantitative sandwich ELISA method and compared.ResultsLevels of all of the studied serum vascular markers were lower in TNFα inhibitors-treated JIA patients than in new-diagnosed. The significant difference was observed in VEGF-R1 levels (0,07±0,02ng/ml vs. 0,1±0,03ng/ml; p<0,05) and VEGF-R2 levels (7,94±1,56ng/ml vs. 15,92±7,09ng/ml; p<0,001).ConclusionsThe study shows the important influence of TNFα inhibitors on angiogenesis in rheumatoid process. The blockade of VEGF receptors and VEGF activity might be of therapeutic benefit in JIA.Disclosure of InterestNone declared

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