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

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.

• Authors: Dovile Sinkeviciute, Solveig Skovlund Groen, Shu Sun, Tina Manon-Jensen, Anders Aspberg, Patrik Önnerfjord, Anne-Christine Bay-Jensen, Salome Kristensen, Signe Holm Nielsen
• Journal: Scientific reports (Sci Rep) Vol. 10 Issue 1 Pg. 13541 (08 11 2020) ISSN: 2045-2322 [Electronic] England
• PMID: 32782251 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• AC133 Antigen
• Antibodies, Monoclonal
• Biomarkers
• Extracellular Matrix Proteins
• Glycoproteins
• PRELP protein, human
• PROM1 protein, human
• Matrix Metalloproteinases

Topics

• AC133 Antigen (metabolism)
• Animals
• Antibodies, Monoclonal (biosynthesis, immunology)
• Antibody Formation
• Arthritis, Psoriatic (blood, diagnosis)
• Biomarkers (blood)
• Case-Control Studies
• Cohort Studies
• Enzyme-Linked Immunosorbent Assay
• Extracellular Matrix Proteins (blood, immunology)
• Female
• Glycoproteins (blood, immunology)
• Humans
• Male
• Matrix Metalloproteinases (metabolism)
• Mice
• Mice, Inbred BALB C
• Middle Aged
• ROC Curve