RANTES is a possible marker of paradoxical psoriatic arthritis.

Abstract

Objectives: Biologic therapies have revolutionised the treatment of psoriasis (PsO) and psoriatic arthritis (PsA), significantly improving patient outcomes. However, paradoxical psoriatic arthritis (PPsA), a condition where biologics exacerbate joint inflammation, has emerged as a rare but concerning adverse effect. This study aimed to investigate the immunological mechanisms underlying PPsA and identify potential biomarkers associated with its development.

Methods: A cohort of 23 patients with PsO, with or without concurrent PsA, who had undergone biologic therapy, was analysed. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with Streptococcus pyogenes to mimic inflammatory outbreaks, followed by ex vivo treatment with the biologics each patient had experienced. Cytokine and chemokine levels were quantified to assess immune responses.

Results: Patients who developed PPsA exhibited a significant elevation in regulated upon activation normal T cell expressed and secreted (RANTES) levels (p = 0.001) after exposure to culprit biologics, compared to those without PPsA. Additionally, a notable decrease in interferon-gamma (IFN-γ) levels was observed, suggesting altered immune dynamics. These findings indicate that RANTES plays a central role in the pathogenesis of PPsA and may serve as a predictive biomarker.

Conclusions: This study highlights the importance of screening for elevated RANTES levels before initiating biologic therapy to mitigate PPsA risk. The results underscore the need for personalised therapeutic approaches and further research into the molecular mechanisms of PPsA, paving the way for safer and more effective treatments.