Neutrophils from patients with SAPHO syndrome show no signs of aberrant NADPH oxidase-dependent production of intracellular reactive oxygen species

Rheumatology (Oxford). 2016 Aug;55(8):1489-98. doi: 10.1093/rheumatology/kew192. Epub 2016 Apr 27.

Abstract

Objective: We aimed to investigate if aberrant intracellular production of NADPH oxidase-derived reactive oxygen species (ROS) in neutrophils is a disease mechanism in the autoinflammatory disease SAPHO syndrome, characterized by synovitis, acne, pustulosis, hyperostosis and osteitis, as has previously been suggested based on a family with SAPHO syndrome-like disease.

Methods: Neutrophil function was explored in a cohort of four patients with SAPHO syndrome, two of whom were sampled during both inflammatory and non-inflammatory phase. Intracellular neutrophil ROS production was determined by luminol-amplified chemiluminescence in response to phorbol myristate acetate.

Results: Cells from all patients produced normal amounts of ROS, both intra- and extracellularly, when compared with internal controls as well as with a large collection of healthy controls assayed in the laboratory over time (showing an extensive inter-personal variability in a normal population). Further, intracellular production of ROS increased during the inflammatory phase. Neutrophil activation markers were comparable between patients and controls.

Conclusion: Dysfunctional generation of intracellular ROS in neutrophils is not a generalizable feature in SAPHO syndrome. Secondly, serum amyloid A appears to be a more sensitive inflammatory marker than CRP during improvement and relapses in SAPHO syndrome.

Keywords: NADPH oxidase; SAPHO syndrome; autoinflammation; granulocytes; inflammation; reactive oxygen species.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Hyperostosis Syndrome / enzymology*
  • Acute-Phase Proteins / metabolism
  • Adolescent
  • Aged
  • Apoptosis / physiology
  • Biomarkers / metabolism
  • Case-Control Studies
  • Cytokines / metabolism
  • Female
  • Humans
  • Male
  • Middle Aged
  • NADPH Oxidases / biosynthesis
  • NADPH Oxidases / metabolism*
  • Neutrophils / enzymology*
  • Reactive Oxygen Species / metabolism*
  • Recurrence
  • Up-Regulation / physiology

Substances

  • Acute-Phase Proteins
  • Biomarkers
  • Cytokines
  • Reactive Oxygen Species
  • NADPH Oxidases