The role of damage-associated molecular pattern for pathogenesis and biomarkers in adult-onset Still’s disease

ABSTRACT

Introduction: Adult-onset Still’s disease (AOSD) is a systemic inflammatory disease, which presents itself as an adult form of systemic juvenile idiopathic arthritis. Innate immune activation driven by a combination of genetic and environmental factors is the primary mechanism underlying disease pathogenesis in AOSD patients. Few biomarkers have been identified for AOSD diagnosis or for the assessment of disease activity or prediction of clinical outcomes. Damage-associated molecular patterns (DAMPs) can activate innate immunity, resulting in tissue damage. Changes in several DAMPs are associated with disease pathogenesis in AOSD patients.

Areas covered: This review describes the role of DAMPs in AOSD pathogenesis and discusses their potential for use as disease biomarkers. Together with overall pathogenesis of AOSD, high-mobility group box-1, advanced glycation end products, S100 proteins, and neutrophil extracellular traps are introduced and discussed in detail.

Expert opinion: The activation of macrophages and neutrophils is associated with several DAMPs, causing high concentrations of proinflammatory cytokines in AOSD patients. Involvement of certain DAMPs in AOSD patients is well documented due to the presence of sterile inflammation; however, direct evidence for some DAMPs is lacking. Further research into the role of DAMP molecules in AOSD patients may reveal new biomarkers and provide targets for disease intervention.

KEYWORDS:

• Damage-associated molecular pattern
• S100A8/A9
• adult-onset Still’s disease
• pathogenesis
• biomarker

Article highlights

• DAMPs play an important role in triggering the innate immune system, including cell activation and cytokine production in AOSD patients.

• S100 protein levels were consistently increased in AOSD patients and correlated with disease activity, indicating their potential as biomarkers for AOSD.

• The release of NETs has been implicated in the pathogenesis of AOSD in a variety of ways. Further studies would provide novel candidates as biomarkers for AOSD.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Data availability statement

The data used to support the findings of this study are included within the article.

Additional information

Funding

This research was supported by a grant from the Korea Health Technology R&D Project, through the Korea Health Industry Development Institute (KHIDI), which is funded by the Ministry of Health & Welfare, Republic of Korea [grant number: HI16C0992].