Inflammasome activation and formation of ASC specks in patients with juvenile idiopathic arthritis

ObjectiveThe formation of large intracellular protein aggregates of the inflammasome adaptor ASC is a hallmark of inflammasome activation and characteristic of autoinflammation. Inflammasome activated cells release the highly proinflammatory cytokine IL-1 beta in addition to ASC specks into the extracellular space. Autoinflammatory activity has been demonstrated in systemic JIA, however minimal data exist on the role of inflammasomes in other JIA subtypes. We therefore investigated, if pyroptotic cells are present in the circulation of oligo- and poly-articular JIA. MethodsPeripheral blood of JIA patients (n = 46) was investigated for ASC speck formation, a key step in inflammasome activation, by flow cytometry and immunofluorescence. Free ASC and proinflammatory cytokine levels were determined by ELISA and multiplex assay. ResultsOligo-articular JIA patients showed a significantly increased proportion of ASC speck(+) monocytes compared to poly-articular JIA patients. In serum free ASC alone is not sufficient to assess inflammasome activity and does not correlate with ASC speck(+) monocytes. Compared to control several cytokines were significantly elevated in samples of JIA patients. JIA serum containing antinuclear antibodies, incubated with ASC specks boosts a secondary inflammation by IL-1 beta production in macrophages. ConclusionFor the first time, we detect ex vivo inflammasome activation by ASC speck formation in oligo- and poly-articular JIA patients. Most notably, inflammasome activation was significantly higher in oligo- compared to poly-articular JIA patients. This data suggests that inflammasome derived autoinflammation may have a greater influence in the previously thought autoimmune oligo-articular JIA patients.

Automated summary

The formation of large intracellular protein aggregates of the inflammasome adaptor ASC is a key step in inflammasome activation and characteristic of autoinflammation. The study investigated the presence of pyroptotic cells in the circulation of oligo- and poly-articular JIA patients, and found that oligo-articular JIA patients showed significantly higher inflammasome activation compared to poly-articular JIA patients. This suggests that inflammasome derived autoinflammation may have a greater influence in oligo-articular JIA patients.