Increased serum caspase-1 in adult-onset Still’s disease

Author:

Matsumoto Haruki1,Yoshida Shuhei1,Koga Tomohiro2,Fujita Yuya1,Sumichika Yuya1,Saito Kenji1,Sato Shuzo1,Asano Tomoyuki1,Mizokami Masashi3,Sugiyama Masaya3,Migita Kiyoshi1

Affiliation:

1. Fukushima Medical University School of Medicine

2. Nagasaki University Graduate School of Biomedical Sciences

3. National Center for Global Health and Medicine

Abstract

Abstract Background Caspase-1 is an essential component in the inflammasome activation cascade. This study assessed the potential of serum caspase-1 level as an inflammatory biomarker in patients with adult-onset Still’s disease (AOSD). Methods The study included 51 consecutive patients diagnosed with AOSD based on the Yamaguchi criteria, 66 patients with rheumatoid arthritis (RA) as a disease control, and 36 healthy subjects. Serum concentrations of caspase-1 were measured using enzyme linked immunosorbent assay (ELISA). In AOSD patients, the serum levels of 69 cytokines were analyzed using a multi-suspension cytokine array, and a cluster analysis of each cytokine was performed to identify specific molecular networks. Results AOSD patients had significantly increased serum caspase-1 levels versus RA patients (p < 0.001) and healthy subjects (p < 0.001). Serum caspase-1 also had significant positive correlations with AOSD disease activity score (Pouchot score r = 0.59, p < 0.001) and serum ferritin (r = 0.54, p < 0.001). Furthermore, among AOSD patients, significant correlations existed between serum caspase-1 and inflammatory cytokines, including IL-18. On immunoblot analysis, the cleaved form of caspase-1 (p20) was detected in the serum of untreated AOSD patients not in those from inactive AOSD patients receiving immunosuppressive treatments. Conclusions Caspase-1 can be a useful biomarker for the diagnosis and monitoring of AOSD. Activation of caspase-1 could be correlated with the inflammatory component of AOSD, specifically through the induction of proinflammatory cytokines via inflammasome activation cascades.

Publisher

Research Square Platform LLC

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