The role of growth factors and osteoclast mediators in the pathogenesis of early untreated juvenile idiopathic arthritis (JIA)

Background: This study forms part of a larger five year prospective study into theprogression and outcome of JIA. The aim was to evaluate the function of growthfactors and osteoclast mediators in the pathogenesis of early untreated disease.Methods: Synovial biopsies were obtained from 41 JIA patients defined accordingto ILAR criteria. They had to be steroid naı¨ve and never treated with diseasemodifying drugs. We report the immunopathology of the oligo and poly populations.The density and distribution of IGF-1, IGF-2, IGF-BP2 and IGF-BP3, OPN, VEGFand markers of the RANK/RANK-L axis were assessed. RT-PCR was alsoperformed on the synovial membrane to assess the expression of growth factorsand osteoclast mediators.Results: Twenty five patients were diagnosed with oligoarticular, and 16 witha polyarticular JIA. The mean age at biopsy was 5 yrs 3 months (range 1yr7m -15yrs). The mean disease duration was 5.3 months (range 1-14 months).By definition of the study inclusion criteria, all had at least one knee involved.Preliminary assessment of all patients highlighted marked expression of RANKand its ligand highly in the lining layer and modestly in the sub-lining layer, but OPGwas not detected. However, modest OPG m-RNA expression within the synovialmembrane was detected.IGF-2 and IGF-BP2 were localised to regions where new vessels wereestablished, and where the angiogenic factors OPN and VEGF were co-locallyexpressed.Conclusions: Our novel study highlighted the expression of growth factors andosteoclast mediators in early untreated JIA. Our analysis of the distinguishingprofiles of potential joint destruction Vs joint repair will be compared to identifydifferences in the expression of these markers within the clinical subgroups.Disclosure: The authors have declared no conflicts of interest.