Proteomic analyses related to inflammation and pain in children with juvenile idiopathic arthritis

Background To explore levels of inflammatory proteins (including cytokines) in plasma samples from children with juvenile idiopathic arthritis (JIA) and their relation to the degree of inflammation and pain. Methods A total of 69 plasma samples were collected from 51 children with JIA (51 at diagnosis in a higher disease activity state, 18 at follow-up in a lower disease activity state) and 18 healthy controls. Relative levels of 92 proteins related to a wide range of biological processes in inflammation were obtained using a proximity extension assay panel. Comparisons between children with and without JIA, in different JIA disease states, by juvenile disease activity score (JADAS 27), and by degree of pain on visual analogue scale (VAS), were performed using parametric and non-parametric statistical methods. Results Nineteen proteins involved in arthritic inflammation, such as interleukin 6 (IL-6) and S100 protein A12 (S100A12), were higher in patients with JIA than controls, seven decreased significantly during treatment, and 18 correlated significantly with JADAS27 score. Three proteins correlated with pain VAS scores in unadjusted analyses: the glial cell line-derived neurotrophic factor (GDNF), transforming growth factor beta (TGFβ), and IL-18R1. Levels of GDNF correlated significantly with pain VAS scores but not with JADAS 27. Conclusions Plasma levels of 18 of 92 tested proteins correlated with degree of disease activity. Levels of GDNF originating from neural cells correlated with pain without correlating to inflammatory degree, suggesting that it may play a role in pain in JIA. Further studies in larger cohorts are warranted.