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.

Combined – whole blood and skin fibroblasts- transcriptomic analysis in Psoriatic Arthritis reveals molecular signatures of activity, resistance and early response to treatment

“…PsA is uniquely characterized by synchronous bone erosions and pathological new bone formation (46). Elevated extracellular matrix (ECM) protein fragments in PsA serum reflect the deregulated bone and cartilage turnover and bear the potential to function as diagnostic biomarkers (46)(47)(48). In agreement with these observations, our study also provided evidence of aberrant collagen metabolism in PsA blood during the active phase of the disease.…”

Robust Rank Aggregation and Least Absolute Shrinkage and Selection Operator Analysis of Novel Gene Signatures in Dilated Cardiomyopathy

“…Data from the Human Protein Atlas (HPA) revealed that PRELP is secreted to the extracellular matrix and may anchor basement membranes to the underlying connective tissue ( 42 ), suggesting its potential function in maintaining normal cellular structure. Besides, previous studies have suggested that PERELP has prognostic value in hepatocellular carcinoma and regulates the extracellular matrix and collagen mineralization in the bone system ( 43 , 44 ).…”

Proteomic profiling of small extracellular vesicles derived from mouse pancreatic cancer and stellate cells: Role in pancreatic cancer

“…Interestingly, there were several proteins (96, 32 and 51 in K_sEVs, P_sEVs and PK_sEVs, respectively), which were present only in the sEV proteome but not in the cellular proteome (Figure 5B). P_sEV-specific proteins included, but were not limited to ECM proteins (Tenascin, Prolargin, LOX) [61][62][63], angiogenetic factors (neuropilin-1, Slit3) [64,65] and catalytic enzymes (DPYD, CNDP2) [66,67]. K_sEV specific proteins included Kras, several Ras-related proteins (Rras, Rap-1a, Rab8a Rab14, Rab18, Ralb) and Ephrin family members (Ephb3, Ephb4, Epha4), which are known to be upregulated in cancer cell-derived sEVs [27].…”