FRI0370 ACCELERATED EXTRACELLULAR MATRIX REMODELING IN PSORIATIC ARTHRITIS &amp; VALUE OF ECM-RELATED BIOMARKERS
Authors: Samra Sardar, Salome Kristensen, Anne Sofie Siebuhr, Jeppe Christensen, Morten Karsdal, Annette Mortensen, Anne-Christine Bay-Jensen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> With our increasing understanding of cross-talk between the immune system (immune cells, cytokines) and extracellular matrix (ECM) of the affected tissues, ECM destruction and turnover has gained a lot of attention in inflammatory arthritis. ECM mainly consists of interstitial matrix (rich in type I and III collagens) and basement membrane (mainly composed of type IV collagen), both of which are affected in inflammatory arthritis. We hypothesize that inflammatory milieu in Psoriatic Arthritis (PsA) leads to accelerated ECM destruction and remodeling, and the release of ECM metabolites into circulation, that can be measured in serum as biomarkers of tissue remodeling and may give insight to pathological process at the tissue level. <h3>Objectives</h3> This prospective study aimed to use serological biomarkers for evaluation of the extent of damage to, and changes in turnover of ECM in patients with PsA and to investigate their relation to inflammatory biomarkers and disease activity. <h3>Methods</h3> Patients with PsA (n=145) fulfilling the CASPAR criteria and above 18 years of age with any disease activity were recruited through outpatient department in Aalborg University Hospital, Denmark. Exclusion criteria were pregnancy, treatment with biological DMARD, or with oral corticosteroids and other comorbidities. Clinical disease parameters were recorded, and blood samples were collected at baseline and 24 weeks follow-up. Inflammation-related ECM remodelling was measured by serological biomarkers of type I, III and IV collagen formation (Pro-C1, Pro-C3 and Pro-C4, respectively) and MMP-mediated degradation (C1M, C3M and C4M respectively). The chronic inflammation was measured by CRPM (MMP degraded metabolite of CRP). All biomarkers were measured by competitive ELISAs and levels were compared to the reference levels of healthy individuals. The biomarker data was log<sub>2</sub> transformed for normalization and standard parametric statistical methods were applied. <h3>Results</h3> We found that there was an increase in the degradation of interstitial matrix (represented by C1M and C3M) which was uncompensated with either decreased (Pro-C1) or unaltered (Pro-C3) formation in patients with PsA as compared to healthy individuals. On the contrary, there was a compensated increase in basement membrane remodeling in patients with PsA as represented by increase in both C4M and Pro-C4 in comparison to healthy individuals (Table 1). Interestingly, there was a strong correlation between baseline C4M and Pro-C4 (r=0.703, p&lt;0.0001), and 24-week changes in both biomarkers (r=0.468, p&lt;0.0001) pointing towards coupling between the two processes which was either lost or was weak in case of interstitial collagens. As baseline values and changes in C1M, C3M, C4M and Pro-C4 showed a strong correlation with changes in inflammatory biomarkers, we believe that ECM remodeling in PsA is, at least partly, driven by inflammation. Furthermore, baseline values and changes in these ECM turnover biomarkers correlated positively with changes in composite disease activity scores (Table 2) that may indicate their clinical importance as potential diagnostic or disease activity markers. <h3>Conclusion</h3> Chronic inflammation underlying PsA pathology results in an increased amount of ECM turnover that correlates with clinical progression and can be measured by serological biomarkers. <h3>References</h3> None <h3>Disclosure of Interests</h3> Samra Sardar Employee of: I am a full time employee at Nordic Bioscience, Salome Kristensen: None declared, Anne Sofie Siebuhr Employee of: I am a full-time employee in Nordic Bioscience, Jeppe Christensen: None declared, Morten Karsdal Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience, Annette Mortensen: None declared, Anne-Christine Bay-Jensen Shareholder of: I own shares of Nordic Bioscience, Employee of: I am a full-time employee in Nordic Bioscience