Collins, ES, Butt, AQ, Gibson, DS, Dunn, M, Fearon, U, van Kuijk, AW, Gerlag, DM, Pontifex, E, Veale, DJ, Tak, PP, Fitzgerald, O and Pennington, SR (2015) A Clinically Based Protein Discovery Strategy to Identify Potential Biomarkers of Response to Anti-TNF-alpha Treatment of Psoriatic Arthritis. Proteomics Clinical Applications, ? . [Journal article]
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PurposePsoriatic arthritis is a systemic inflammatory and chronic autoimmune disorder that can be treated using biologic therapies that involves targeting of biomolecules such as tumour necrosis factor alpha (TNF-α), interleukins (IL) IL-17 and IL-23. Although 70% psoriatic arthritis patients who receive the TNF-α therapy respond well and get treated successfully, however 30% of patients show either no response or limited clinical improvement. Biomarkers that could predict response to anti-TNF-α therapy in individual patients would help to avoid unnecessary use of expensive biologics in potentially non-responding patients where they are unlikely to be effective. This would enable alternative treatments targeting other biologics to be explored within the relatively narrow (timeframe) window of therapeutic opportunity available. Experimental designPatient synovial tissue samples from two clinical studies were used for (Difference In Gel Electrophoresis) gel-based proteomics to identify changes in protein expression in response to anti-TNF-α treatment. Subsequently multiplexed multiple-reaction-monitoring (MRM) measurements were used to support verification of potential biomarkers.ResultsA number of differences in synovial protein expression were observed between patients who responded or did not respond to anti-TNF-α alpha treatment. A total of 119 protein spots changed significantly (p<0.05) in response to treatment and 25 spots were different (p<0.05) between “good responders” and “poor responders”. Of these, 14 proteins were identified and the development of multiple reaction monitoring assays to explore their potential as predictive biomarkers was initiated.Conclusions and clinical relevanceA gel-based proteomics strategy has demonstrated that anti-TNF-α treatment causes detectable and distinct changes in protein expression in synovial tissue of patients with psoriatic arthritis. The development of a signature of such proteins and a multiplexed assay to measure them may make it possible to predict patient response to anti-TNF-α therapy and allow alternative, more effective, treatments to be explored sooner.
|Item Type:||Journal article|
|Keywords:||Psoriatic arthritis, anti-TNF-α, biomarkers, synovium, proteomics|
|Faculties and Schools:||Faculty of Life and Health Sciences > School of Biomedical Sciences|
Faculty of Life and Health Sciences
|Research Institutes and Groups:||Biomedical Sciences Research Institute|
Biomedical Sciences Research Institute > Stratified Medicine
|Deposited By:||Dr David Gibson|
|Deposited On:||02 Jul 2015 14:44|
|Last Modified:||02 Jul 2015 14:44|
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