A novel biomarker of MMP-cleaved prolargin is elevated in patients with psoriatic arthritis

Dovile Sinkeviciute,Signe Holm Nielsen,Tina Manon-Jensen,Anders Aspberg,Anne-Christine Bay-Jensen,Shu Sun,Solveig Skovlund Groen,Patrik Önnerfjord,Salome Kristensen

doi:10.1038/s41598-020-70327-0

Abstract

Psoriatic arthritis (PsA) is a chronic musculoskeletal inflammatory disease found in up to 30% of psoriasis patients. Prolargin—an extracellular matrix (ECM) protein present in cartilage and tendon—has been previously shown elevated in serum of patients with psoriasis. ECM protein fragments can reflect tissue turnover and pathological changes; thus, this study aimed to develop, validate and characterize a novel biomarker PROM targeting a matrix metalloproteinase (MMP)-cleaved prolargin neo-epitope, and to evaluate it as a biomarker for PsA. A competitive ELISA was developed with a monoclonal mouse antibody; dilution- and spiking-recovery, inter- and intra-variation, and accuracy were evaluated. Serum levels were evaluated in 55 healthy individuals and 111 patients diagnosed with PsA by the CASPAR criteria. Results indicated that the PROM assay was specific for the neo-epitope. Inter- and intra- assay variations were 11% and 4%, respectively. PROM was elevated (p = 0.0003) in patients with PsA (median: 0.24, IQR: 0.19–0.31) compared to healthy controls (0.18; 0.14–0.23) at baseline. AUROC for separation of healthy controls from PsA patients was 0.674 (95% CI 0.597–0.744, P < 0.001). In conclusion, MMP-cleaved prolargin can be quantified in serum by the PROM assay and has the potential to separate patients with PsA from healthy controls.

Highlights

Psoriatic arthritis (PsA) is a chronic musculoskeletal inflammatory disease found in up to 30% of psoriasis patients
Some studies suggest serum interleukin (IL)-2, IL-10, MMP3 and vascular endothelial growth factor (VEGF) may be used to discriminate patients with PsA from patients with psoriasis[14]. Collagen fragments, such as a released N-terminal pro-peptide of type II collagen (PRO-C2) have been shown to be increased in patients with PsA compared to healthy controls, potentially allowing for screening of the d isease[16]
Classification Criteria for Psoriatic Arthritis (CASPAR criteria)[31] are used for providing guidance to the clinicians and for enrolling patients in clinical trials, we need biomarkers to better account for the diverse clinical presentation of PsA and to facilitate personalized medicine

Summary

Introduction

Psoriatic arthritis (PsA) is a chronic musculoskeletal inflammatory disease found in up to 30% of psoriasis patients. MMP-cleaved prolargin can be quantified in serum by the PROM assay and has the potential to separate patients with PsA from healthy controls. Psoriatic arthritis (PsA) is an inflammatory chronic joint disease that is found in up to 30% of psoriasis patients and can precede the skin manifestations of the d isease[1,2]. Some studies suggest serum interleukin (IL)-2, IL-10, MMP3 and vascular endothelial growth factor (VEGF) may be used to discriminate patients with PsA from patients with psoriasis[14] Collagen fragments, such as a released N-terminal pro-peptide of type II collagen (PRO-C2) have been shown to be increased in patients with PsA compared to healthy controls, potentially allowing for screening of the d isease[16]

Objectives

Methods

Results

Conclusion