Background/Purpose: Psoriasis (PsO) is a chronic immune-mediated skin disease. Around 30% of patients diagnosed with PsO will develop psoriatic arthritis (PsA). Patients with PsA may develop irreversible joint damage, therefore optimized screening methods identifying the patients with PsO in risk of developing PsA have become a medical priority. In the interstitial matrix of bone and soft tissue, type I collagen is the most abundant collagen and secreted by fibroblasts. During extracellular matrix (ECM) remodeling, proteases cleave type I collagen resulting in the release of metabolites into the circulation. These collagen metabolites can be quantified in serum as biomarkers of tissue remodeling and give insight to pathological process at tissue level. In this study we investigated type I collagen turnover by measuring synthesis (PRO-C1) and degradation (C1M) biomarkers in a preclinical Scar-in-a-Jar (SiaJ) model and in serum from patients with PsO or PsA.

Methods: In the SiaJ model, primary human healthy dermal fibroblasts were grown for up to 17 days in DMEM medium containing 0.4% fetal calf serum, Ficoll (to produce a crowded environment) and ascorbic acid. Cells were treated with tumor necrosis factor β1 (TGF-β1) [1 nM] and a range of Tofacitinib concentrations [0-100 nM]. Media and treatments were changed twice a week and untreated cell were used as control. PRO-C1 was quantified in the tissue culture supernatant by ELISAs (Nordic Bioscience).  Furthermore, patients with PsO (n=30, mean age 41.1) and patients with PsA (n=30, mean age 50.3) were recruited through St. Vincent’s University Hospital, Ireland. Study was ethically approved by their local ethics committee. Clinical disease parameters were recorded. PRO-C1 and C1M were measured in serum by ELISAs (Nordic Bioscience). Statistical analysis included one-way ANOVA on data from SiaJ model and Mann Whitney test on clinical data from patients with PsO or PsA.

Results: In the dermal fibroblasts, TGF-β1 significantly increased PRO-C1 levels compared to w/o (p<0.001). Moreover, above a concentration of 12.5nM, Tofacitinib decreased TGF-β1 induced type I collagen formation in a dose-dependent manner. The highest treatment concentration of Tofacitinib (100 nM) significantly decreased PRO-C1 to the level of controls (p< 0.001). In the clinical study, PRO-C1 levels were not different between patients with PsO and PsA (p=0.123). However, levels of C1M were elevated in patients with PsA (p=0.029) compared to PsO. The tissue turnover of type I collagen in the interstitial network-system was analyzed (PRO-C1/C1M). Patients with PsO demonstrated increased formation of type I collagen (p=0.007) compared to PsA.

Conclusion: We demonstrated that Tofacitinib decreased collagen type I production in dermal fibroblasts. Moreover, the tissue turnover profile of type I collagen in PsO patients was significantly increased compared to PsA patients, with balance toward tissue formation. The increased type I collagen formation may be due to the dermal fibroblast activity in PsO producing extensive amounts of PRO-C1. These results suggest that serological biomarkers may be used to separate PsO and PsA patients and potentially be used to identify the 30% of PsO patients that progress to PsA.  

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/neo-epitopes-of-type-i-collagen-can-be-utilized-as-translational-biomarkers-for-skin-and-joint-turnover-in-patients-with-psoriasis-and-psoriatic-arthritis/