An explorative study on proteomic analyses related to inflammation and pain in children with juvenile idiopathic arthritis

Abstract

Background Our aim was attempting to find proteins involved in the pain process and correlating with pain but not degree of inflammation in children with juvenile idiopathic arthritis (JIA), using a proteomics panel. Methods A total of 87 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 disease categories, by juvenile disease activity score (JADAS27) and degree of pain on a 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, were higher in patients with JIA than controls, seven decreased significantly during treatment, and 18 correlated significantly with JADAS27. Three proteins correlated with pain VAS scores in unadjusted analyses: the glial cell line-derived neurotrophic factor (GDNF), transforming growth factor beta, and IL-18R1. Levels of GDNF correlated significantly with pain VAS scores but not with JADAS27. Conclusions Plasma levels of 18 of 92 tested proteins correlated with degree of disease activity. Levels of three proteins correlated with pain, and levels of one, GDNF, originating from neural cells, correlated with pain without correlating with inflammatory degree, suggesting that it may play a role in pain in JIA. Further studies in larger cohorts are warranted.

Level of glial cell derived neurotrophic factor in the blood plasma of rheumatoid arthritis patients and its relationship with alexithymia

“…Higher levels of RA activity, pain intensity and worse functional capacity and health status of patients were associated with a higher level of GDNF – generally in line with data from research by Elfving et al; the authors found that the level of GDNF in the plasma of RA patients was higher than in the control group and correlated with the severity of the pain syndrome [ 27 ]. At the same time the available studies testify to the complex and ambiguous nature of the physiological function of GDNF [ 28 ], and in evaluating the regularities, one should take into account as many relevant factors as possible that can influence the effects of GDNF.…”

“…Interpreting the data of our study, one should take into account the report of Lundborg et al that the level of GDNF in chronic pain increased intrathecally but decreased in blood plasma [25], as well as the data of Hulander et al, indicating that a reduced serum level of GDNF may lead to reduced activation of inflammatory pathways and that GDNF expression is significantly modulated by external influences [26]. Higher levels of RA activity, pain intensity and worse functional capacity and health status of patients were associated with a higher level of GDNF -generally in line with data from research by Elfving et al; the authors found that the level of GDNF in the plasma of RA patients was higher than in the control group and correlated with the severity of the pain syndrome [27]. At the same time the available studies testify to the complex and ambiguous nature of the physiological function of GDNF [28], and in evaluating the regularities, one should take into account as many relevant factors as possible that can influence the effects of GDNF.…”