Background Imbalance between cells secreting IL-17 (Th17) and regulatory T lymphocytes (Tregs) may be a key pathogenic event in development of autoimmnune diseases. Recent studies suggest that vitamin D may have a significant impact on the development of autoimmunity, but the problem has been poorly explored in juvenile idiopathic arthritis (JIA) so far.
Objectives In this study we assessed correlation between Tregs, Th17 cells, as well as some immunological parameters and vitamin D metabolites in de novo JIA patients.
Methods Fifty freshly diagnozed JIA children were evaluated. The control group comprised 28 children free from inflammatory conditions. Subpopulations of Tregs and Th17 cells in peripheral blood (PB) (JIA, controls) and in JIA synovial fluid (SF), were determined by flow cytometry. Serum concentrations of IL-1β, IL-6, IL-17, IL-21, IL-23 and TNF-α cytokines were assessed by ELISA. 1,25(OH)2D and 25(OH)D levels were determined by radioimmunoassay and ELISA, respectively. The potential correlation of the results with clinical (JIA activity, type of onset) and laboratory parameters were examined.
Results The proportion of JIA PB Th17 cells was significantly higher than in healthy children (p=0.01). There was no relationship between Treg and Th17 frequency and JIA activity. In JIA PB, but no in SF, a significant relationship between Tregs and platelet levels was observed (p=0.028). Serum levels of IL-1β, IL-6, IL-17, IL-23 were found significantly higher in JIA than in controls (p=0.011, p=0.007, p=0.008 and p=0.023, respectively). The highest serum IL-6 levels were observed in JIA oligoarthritis (p=0,031). In turn, SF IL-21 concentration was distinctly higher in polyarticular subtype of the disease. Significantly higher levels of TNF-α, IL-1β and IL-6 in JIA SF, as compared to JIA PB were observed (p=0.038, p=0.013 and p<0.001, respectively). There was significant correlation between IL-6 and Tregs in PB (R=0.31, p=0.020). Serum 1,25(OH)2D levels in JIA was significantly lower than in the controls (p=0.004), whereas concentrations of 25(OH)D in both groups were comparable. The highest serum levels of both 1,25(OH)2D and 25(OH)D were found in oligoarthritis subtype of JIA. There was significant correlation between serum 1,25(OH)2D and IL-21 levels (p=0.031). No correlation was found between Tregs and Th17 in PB and SF and serum vitamin D levels in JIA.
Conclusions Association between serum 1,25(OH)2D and IL-21 levels may indicate immunomodulatory role of vitamin D in JIA development. Correlation between serum IL-6 and PB Tregs ratios confirms the role of this cytokine in the maintenance of Th17/Treg cell balance in JIA. Taking together, these results strongly suggest activation of PB/SF Th17 cells and vitamin D deficiency in children with JIA, which may be responsible, along to high TNF-α, IL-1β, IL-6 and IL-17 SF levels, for the development of autoimmunity and initiation of local, chronic inflammation in the joints.
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Acknowledgements The study was supported by the grant from Medical University of Lodz, Poland No 502-03/8-000-01/502-64-055.
Disclosure of Interest None Declared
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