An explorative study on proteomic analyses related to inflammation and pain in children with juvenile idiopathic
Andreas Elfving1, Arja Harila-Saari1, Ludwig Nilsson1
1Department of Women's and Children's Health, Uppsala University, 75185, Uppsala, Sweden.
Insights
Researchers identified glial cell line-derived neurotrophic factor (GDNF) as a protein correlating with pain in juvenile idiopathic arthritis (JIA) but not inflammation. This finding may offer new insights into JIA pain mechanisms.
Area of Science:
- Proteomics
- Pediatric Rheumatology
- Pain Research
Background:
- Juvenile idiopathic arthritis (JIA) involves chronic inflammation and pain in children.
- Identifying specific pain biomarkers independent of inflammation is crucial for targeted therapies.
Purpose of the Study:
- To discover proteins associated with pain in JIA, distinct from inflammatory markers.
- To utilize a proteomics panel for comprehensive protein analysis in JIA patients.
Main Methods:
- Analyzed plasma samples from 51 children with JIA and 18 healthy controls using a proximity extension assay.
- Measured relative levels of 92 inflammation-related proteins.
- Correlated protein levels with disease activity (JADAS27) and pain (VAS) scores.
Main Results:
- Nineteen proteins were elevated in JIA patients; 18 correlated with disease activity (JADAS27).
- Three proteins, including glial cell line-derived neurotrophic factor (GDNF), correlated with pain (VAS).
- GDNF levels significantly correlated with pain but not JADAS27, suggesting a pain-specific role.
Conclusions:
- GDNF is a potential biomarker for pain in JIA, independent of inflammatory disease activity.
- Further investigation in larger cohorts is needed to validate GDNF's role in JIA pain.
- Proteomics offers a valuable approach to understanding complex disease mechanisms like JIA pain.
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.
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