Psoriatic arthritis under a proteomic spotlight: application of novel technologies to advance diagnosis and management.

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.

Cancer and viruses: a double-edged sword.

Oncovirus, synonymously called a 'tumour virus', is a virus that can cause cancer. An oncolytic virus preferentially infects the host's cancer cells and lyses them, causing tumour destruction, and is thus referred to as a 'cancer killing virus'. With an estimated 11% of cancer-associated deaths caused by oncoviruses and the possibility that many cancers may be treated by using oncolytic viruses, the role of viruses in cancer may be viewed as a double-edged sword. A total of seven human cancer viruses have been identified as oncoviruses, having been associated with various cancers. Conversely, a large number of oncolytic viruses have shown great potential towards the treatment of certain types of cancer. Proteomics has now been applied towards understanding the complex interplay that exists between oncoviruses and the immune responses that serve to prevent oncoviral diseases. This review attempts to summarise the neoplastic potential of human tumour associated viruses and associated vaccine successes. The potential use of oncolytic viruses for the therapeutic intervention of cancer will also be discussed. Finally, this review will discuss the enormous potential of proteomics technology in the field of oncovirology.

A clinically based protein discovery strategy to identify potential biomarkers of response to anti-TNF-α treatment of psoriatic arthritis.

PURPOSE: Psoriatic arthritis (PsA) can be treated using biologic therapies targeting biomolecules such as tumor necrosis factor alpha, interleukins (IL)-17 and IL-23. Although 70% PsA patients respond well to therapy, 30% patients show no or limited clinical improvement. Biomarkers that predict response to therapy would help to avoid unnecessary use of expensive biologics in nonresponding patients and enable alternative treatments to be explored. EXPERIMENTAL DESIGN: Patient synovial tissue samples from two clinical studies were analysed using difference in-gel electrophoresis-based proteomics to identify protein expression differences in response to anti-TNF-α treatment. Subsequent multiplexed MRM measurements were used to verify potential biomarkers. RESULTS: A total of 119 proteins were differentially expressed (p<0.05) in response to anti-TNF-α treatment and 25 proteins were differentially expressed (p<0.05) between "good responders" and "poor responders". From these differentially expressed proteins, MRM assays were developed for four proteins to explore their potential as treatment predictive biomarkers. CONCLUSION AND CLINICAL RELEVANCE: Gel-based proteomics strategy has demonstrated differential protein expression in synovial tissue of PsA patients, in response to anti-TNF-α treatment. Development of multiplex MRM assays to these differentially expressed proteins has the potential to predict response to therapy and allow alternative, more effective treatments to be explored sooner.