Hyaluronan concentration and molecular mass in psoriatic arthritis: biomarkers of disease severity, resistance to treatment, and outcome

Abstract

Objective: Low molecular mass hyaluronan causes inflammatory processes and can act as a pro-inflammatory cytokine in skin and other sites of activity in psoriatic arthritis (PsA). This study investigated whether the molecular mass distribution of hyaluronan (HA) in skin and the quantity of circulating HA are related to the clinical inflammatory picture in PsA with active disease and to the effect of treatment with anti-tumour necrosis factor-α (anti-TNF-α) adalimumab. Methods: Twenty patients with TNF-α-naïve active polyarticular PsA were included in this prospective clinical trial of treatment with 40 mg s.c. adalimumab according to standard procedure. Clinical activity, patients' assessments, and skin biopsies were captured at inclusion and at the 12 week follow-up. Ten healthy individuals were recruited for comparison of HA analyses. Histochemistry of skin inflammation, serum HA, and molecular mass of HA were determined. Results: Overall improvements in clinical parameters were observed. Eight of 18 patients reached minimum disease activity after 12 weeks and disease activity was significantly reduced (p < 0.0001). Patients with elevated serum HA values were significantly older, had later onset of arthritis and more deformed joints, still had swollen joints after treatment, and had more circulating inflammatory biomarkers. More severe disease pathology showed a wide spectrum of high-molecular-mass HA accompanied by low mass HA. The treatment appears partly to normalize the HA mass distribution. Conclusion: HA concentration and mass seem to be two possible factors in the inflammatory pathology of PsA acting as biomarkers for disease severity, resistance to treatment, and worse outcome.

Biomarkers predictive of treatment response in psoriasis and psoriatic arthritis: a systematic review

“…measured skin inflammation, serum hyaluronan (HA) and molecular mass of HA in patients subsequently treated with adalimumab. 47 Patients with elevated HA values had more retained swollen joints and higher overall disease activity after 12 weeks of treatment. Muramatsu et al .…”

Deciphering Gut Microbiota Dysbiosis and Corresponding Genetic and Metabolic Dysregulation in Psoriasis Patients Using Metagenomics Sequencing

“…The reduced generation of butyrate in psoriasis patients may compromise the integrity of the intestinal epithelial barrier, resulting in immune responses and chronic inflammation (Bischoff et al, 2014;Christensen et al, 2018;Shapiro et al, 2019). It has been reported that hyaluronan can act as a pro-inflammatory cytokine and induce inflammatory processes in psoriatic arthritis (Hellman et al, 2019). The VEGF signaling pathway plays an important role in psoriasis, and modified hemicellulose suppresses VEGF-induced angiogenesis (Malecic and Young, 2016;Zhu et al, 2017).…”

Association between inflammasome-related polymorphisms and psoriatic arthritis

“…Several possible mechanisms have been suggested to be involved in the aetiology, disease expression, and prognosis of PsA, such as different genetic and environmental factors. Other mechanisms have also been of interest; for example, hyaluronan expression seems to be a possible factor in the inflammatory pathology of PsA acting as a biomarker for disease severity, resistance to treatment, and worse outcome (7). The present study focuses on genes related to inflammasomes.…”