engleski

Damage-associated molecular pattern (DAMP) molecules as mediators of systemic juvenile idiopathic arthritis

Introduction: Systemic juvenile idiopathic arthritis (sJIA) is chronic childhood arthritis of unknown cause. Novel studies seem to point to deregulation of the innate immune system as the primary pathophysiological mechanism, thus making sJIA an auto-inflammatory disorder. Aim: To explore the involvement of alarmins in the pathogenesis of sJIA Patients and methods: We harvested peripheral blood mononuclear cells from the 13 sJIA patients (mean age (±SD) 7.7 ± 5.0 ; 7 girls, 7 boys) at the first admission, as well as from the healthy age- and sex-matched controls, and determined the expression of genes for high mobility box group 1 (HMGB-1), S100A12, and receptor for advanced glycation end-products (RAGE). Results: As expected the expression of S100A12 was significantly higher in sJIA children (median and interquartile range in JIA 1.60 (2.70), in controls 0.51 (0.43) ; P < 0.01 ), while the levels of HMGB-1 were unexpectedly low (median and interquartile range in JIA 0.21 (0.20), in controls 0.47 (0.11) ; P < 0.01). There was no difference in the expression of RAGE between the groups and, moreover, its levels were generally quite low, approaching the detection limit. In the line with the gene expression data, the levels of HMGB-1 showed close inverse relationship with ESR, CRP levels, and the total leukocyte counts (Spearman’s rho from -0.55 to -0.68), while S100A12 showed close correlated well with CRP (rho = 0.42) and leukocytes (rho = 0.46). Conclusion: Therefore, although both HMGB-1 and S100A12 could play a role in the pathogenesis of sJIA, it seems that the patients could potentially benefit only from the intervention into S100 pathway. Although more data are needed to get a good insight, we believe that the present results provide a useful foundation for further studies.

alarmins; juvenile idiopathic arthritis

nije evidentirano