Angiogenic markers in difficult-to-treat psoriatic arthritis.

BACKGROUND: Difficult-to-treat (DTT) psoriatic arthritis (PsA) is characterized by persistent disease activity despite treatment with multiple advanced therapies. Angiogenesis and extracellular matrix remodeling are key processes in chronic inflammatory arthritis, with CD147 acting as an important regulator. OBJECTIVE: Our aim was to evaluate the circulating pro- and anti-angiogenic mediators and inflammatory cytokines in patients with DTT PsA compared with non-DTT PsA controls. METHODS AND RESULTS: Serum samples from 22 patients with DTT PsA were compared with matched samples from 25 non-DTT PsA patients who were on biologics or targeted therapies (non-DTT Bio) and with 25 non-DTT PsA patients who were naive to biologics and targeted therapies and received conventional disease-modifying antirheumatic drugs (cDMARDs) or non-steroidal anti-inflammatory drugs (NSAIDs) (non-DTT cDMARDs). The concentrations of angiogenic factors and inflammatory cytokines were determined with ELISA. Compared with both control groups, patients with DTT PsA demonstrated significantly higher serum levels of CD147 and increased activities of MMP-9 and proteasome 20S, which were measured by the cleavage of their respective fluorescent substrates. The levels of vascular endothelial growth factor (VEGF), TIMP-1, endostatin, and thrombospondin-1 (Tsp-1) did not differ significantly. The scratch assay with diluted serum samples, which was used to measure the ability of endothelial cells to migrate and close the gap, revealed enhanced angiogenic potential in the DTT group relative to the two control groups. In contrast, no differences between the groups were revealed in the serum levels of IL-17, IL-23, IL-22, IL-6, TNF-α, and TGF-β, and only IL-12p70 was reduced in the DTT relative to the control groups. The CD147 levels increased over time exclusively in the DTT PsA group. CONCLUSIONS: An enhanced angiogenic profile, highlighted by an elevated CD147, was found in patients with DTT PsA compared with non-DTT patients, requiring further studies to better understand its role in the pathogenesis of and as a biomarker in PsA.