Psoriatic Arthritis Under a Proteomic Spotlight: Application of Novel Technologies to Advance Diagnosis and Management

Abstract

Psoriatic arthritis is a form of inflammatory arthritis that is frequently associated with psoriasis. Individuals with this disease present with heterogeneous clinical manifestations, making it challenging to diagnose and select optimal treatment strategies. Perhaps, not unsurprisingly, there are currently no molecular diagnostic or prognostic tests to confirm if a patient has the disease or predict how they may respond to therapy. Instead, a range of classification criteria have been developed, and the experience of the treating clinician is heavily relied upon. It is therefore widely accepted that there is a significant and as yet unmet need for effective molecular markers in psoriatic arthritis. Protein mediators drive disease pathogenesis and, therefore, represent logical potential biomarkers. Indeed, significant advances have recently been made by the introduction of multiplexed protein biomarker tests for monitoring disease activity in rheumatoid arthritis. At the same time, recent advances in proteomics have enhanced the capabilities for the detection and discovery of protein biomarkers. These advances offer renewed opportunities for the development of multi-protein biomarker signatures to support clinical decision-making in the diagnosis, prognosis and treatment of psoriatic arthritis. This review summarises the pathogenesis of psoriatic arthritis, highlighting specific areas of unmet clinical need. Furthermore, it seeks to illustrate how the latest developments in proteomic technologies could be used to enhance our understanding of the molecular pathology of psoriatic arthritis and improve clinical outcomes and quality of life for patients.

Urinary proteomics can define distinct diagnostic inflammatory arthritis subgroups

“…It is not possible to directly compare the peptides identified in this study with those in previously published studies for a number of reasons. Firstly, the vast majority of previous studies evaluated peptides in serum, synovial fluid or tissue (for example cartilage, skin, synovial biopsies) 18 19 20 . Biomarkers present in these specimens would not be expected to be present in urine in an unmodified manner.…”

“…Biomarkers present in these specimens would not be expected to be present in urine in an unmodified manner. These previous studies also focused largely on using proteomics to identify biomarkers of disease activity or treatment response rather than for diagnostic purposes 18 19 20 21 . Furthermore, the differentially expressed peptides identified will depend on which condition they are being compared to, and in our case this was a unique combination of four other conditions for each condition.…”

Pathogenesis of psoriasis in the “omic” era. Part III. Metabolic disorders, metabolomics, nutrigenomics in psoriasis in psoriasis

“…Untargeted analysis provides a global picture of metabolic or proteomic activity and was used to differentiate between the healthy people and psoriasis patients, proposing new targets for diagnosis or metabolism understanding. Targeted analysis concentrates on metabolite or protein of interest for precise measurement for diagnostic, prognostic or drug treatment monitoring [78] ( Figure 5 and Table 2).…”

“…Proteomics provide the information about protein identification and differentiation in disease progression using different separation techniques coupled with mass spectrometry. The main purpose of proteomic studies is to define novel biomarkers for diagnostics, monitoring and prognostics of psoriasis [ 75 – 78 ]. Figure 4 represents some of the observed changes in protein distribution in psoriasis disease in skin, plasma and urine samples.…”

“…Proteomic changes in psoriasis[75][76][77][78][79][80] Biomarker discovery Plasma Desmoplakin, complement C3, polymeric immunoglobulin receptor and cytokeratin 17 correlate with the PASI score and could serve as the novel biomarkers for the disease severityProfilin 1 had a tendency to increase in the psoriatic plasma Skin Neural cell adhesion molecule L1 (L1CAM/CD171) and dipetidyl peptidase 4 (DDP4/CD26), could serve as the novel biomarkers for human skin mast cells in normal, psoriatic and mastocytosis skin Novel mechanism Plasma Proteins involved in lipid metabolism and vitamin D regulation Proteins involved in the immune response and signal transduction Cytoskeletal and actin-binding, proteins/petides and Ca 2+ -binding components suggests disease-related cell leakage and altered protease activity Skin Glutathione S transferase 1, peroxiredoxin 2 and SFN protein, abnormalities in cell proliferation, the regulatory/balancing system and the inflammatory response Proteome profile of acute psoriasis and contact eczema are similar but different from chronic plaque psoriasis, duration of the disease process may affect the skin proteome pattern A. Owczarczyk-Saczonek, D. Purzycka-Bohdan, B. Nedoszytko, A. Reich, A. Szczerkowska-Dobosz, J. Bartosińska, A. Batycka-Baran, R. Czajkowski, I.T. Dobrucki, L.W.…”