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

PLoS One. 2024 Jul 29;19(7):e0307908. doi: 10.1371/journal.pone.0307908. eCollection 2024.

Abstract

Background: Caspase-1 is a crucial component in the inflammasome activation cascade. This study evaluated 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 disease control, and 36 healthy controls (HCs). Serum caspase-1 concentrations were measured using enzyme-linked immunosorbent assay. The serum 69 cytokine levels were analyzed using a multisuspension cytokine array in patients with AOSD, and a cluster analysis of each cytokine was performed to determine specific molecular networks.

Results: Patients with AOSD had significantly increased serum caspase-1 levels versus patients with RA (p < 0.001) and HCs (p < 0.001). Additionally, serum caspase-1 demonstrated 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 patients with AOSD, significant correlations existed between serum caspase-1 and inflammatory cytokines, including interleukin-18. Immunoblot analysis detected the cleaved form of caspase-1 (p20) in the serum of untreated patients with AOSD, not in those from patients with inactive AOSD receiving immunosuppressive treatments.

Conclusions: Caspase-1 is a useful biomarker for AOSD diagnosis and monitoring. Caspase-1 activation could be correlated with the inflammatory component of AOSD, specifically through proinflammatory cytokine induction via inflammasome activation cascades.

MeSH terms

  • Adult
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis
  • Biomarkers* / blood
  • Case-Control Studies
  • Caspase 1* / blood
  • Cytokines / blood
  • Female
  • Humans
  • Interleukin-18 / blood
  • Male
  • Middle Aged
  • Still's Disease, Adult-Onset* / blood
  • Still's Disease, Adult-Onset* / diagnosis

Substances

  • Caspase 1
  • Biomarkers
  • Interleukin-18
  • Cytokines

Grants and funding

The study was supported by the Japan Grant-in-Aid for Scientific Research (20K08777).The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.