An update on pathogenesis of psoriatic arthritis and potential therapeutic targets

ABSTRACT

Introduction: Innate immune response and bone remodeling are key factors contributing to the pathogenesis of psoriatic arthritis (PsA). Moreover, the evidence of autoantibodies in patients’ sera suggests an autoimmune side in PsA. Besides the immune pathways, studies strongly support the role of genetic risk alleles in affecting the clinical heterogeneity of PsA as well as the response to therapy. A good clinical response to treatment, indeed, represents a challenge in PsA patients and the identification of patient-targeted therapies is still a critical issue.

Areas covered: We performed a systematic review aiming at describing new evidence on PsA pathogenesis and treatments. Reported items for systematic reviews (PRISMA checklist) were analyzed. Studies included from the PubMed database addressed the following items: innate immunity, autoimmunity, bone remodeling, and therapeutic targets in PsA; time frame of research 1970–2019. Specifically, we reviewed data on IL-17 inhibitors, abatacept, JAK inhibitors, ABT 122, and A (3) adenosine receptors agonist, CF101.

Expert opinion: In PsA an intriguing pathogenetic network has been documented. Several biological and synthetic drugs are promising in terms of efficacy and safety profile.

KEYWORDS:

• Psoriatic arthritis
• innate immunity
• bone remodeling
• target therapies

Article Highlights

1. Intricate interactions between genetic predisposition, environmental triggers, and innate immune system activation give rise to an autoimmune footprint in PsA pathogenesis;

2. LL37 is an antimicrobial peptide upregulated in psoriatic skin and anti-LL-37 autoantibodies were significantly elevated in PsA suggesting a role of anti-LL37 antibodies as a pathogenetic biomarker in PsA;

3. Among environmental factors, trauma and stress are well related to PsA pathogenesis, but more recently, factors as obesity, gut dysbiosis, infections, and smoke have been taken into consideration in PsA pathogenesis;

4. The peculiar clinical feature in PsA is the bone loss associated to osteoproductive phenomena, with eccentric bone erosions, syndesmophytes, and ankylosis. The pathogenic pathways responsible for this unique bone remodeling are regulated by the interplay between Osteoblast and Osteoclasts;

5. Tailoring bDMARD therapy to maximize outcomes, safety, and cost-effective care is a key target in the management of PsA.

Acknowledgments

The authors would like to thank Dr. Laura Mattew for the language editing.

Declaration of interest

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

The paper was not funded