HMGB1 Levels Are Increased in Patients with Juvenile Idiopathic Arthritis, Correlate with Early Onset of Disease, and Are Independent of Disease Duration

Objective. High mobility group box chromosomal protein 1 (HMGB1) has been implicated as a mediator of inflammation in rheumatoid arthritis (RA), while its role in juvenile idiopathic arthritis (HA) has not been described. To evaluate the role of HMGB1 in the inflammatory process in HA and its potential as a therapeutic target, we investigated whether extracellular HMGB1 is detectable in HA and if so, to correlate the levels with established inflammatory markers and clinical measures. Methods. Matching samples of blood and synovial fluid (SF) were collected from 23 patients with HA. Levels of HMGB1, soluble receptor for advanced glycation endproducts, S100A12, myeloid-related protein 8/14, and other inflammatory mediators were analyzed. Results. Significantly increased HMGB1 levels were recorded in SF compared to blood samples from patients with HA. The amount of HMGB1 was highest in patients with early disease onset irrespective of disease duration. In contrast, the proinflammatory S100 protein and interleukin 8 were highest in patients in early phases of disease. Matrix metalloproteinase-3, a marker of cartilage destruction, was higher in patients with late disease onset, indicating similarities with RA in that patient subgroup. Conclusion. Levels of extracellular HMGB1 are increased in the inflamed joints of patients with HA. This warrants further studies of HMGB1 as a mediator of JIA pathogenesis as well as a biomarker for inflammatory activity and as a target for therapy. The variation in levels of HMGB1 and S100 proteins in relation to disease onset indicates a difference in inflammatory phenotype during disease progression.