title: A clinically based protein discovery strategy to identify potential biomarkers of response to anti-TNF-α treatment of psoriatic arthritis.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.|Department of Rheumatology, St Vincent's University Hospital, Elm Park, Dublin, Ireland.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Collins
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Aisha Q
authors.initials: AQ
authors.lastname: Butt
authors.affiliation: Northern Ireland Centre for Stratified Medicine, University of Ulster, C-TRIC, Londonderry, UK.
authors.forename: David S
authors.initials: DS
authors.lastname: Gibson
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Dunn
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.|Department of Rheumatology, St Vincent's University Hospital, Elm Park, Dublin, Ireland.
authors.forename: Ursula
authors.initials: U
authors.lastname: Fearon
authors.affiliation: Department of Clinical Immunology and Rheumatology, F4-105, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Arno W
authors.initials: AW
authors.lastname: van Kuijk
authors.affiliation: Department of Clinical Immunology and Rheumatology, F4-105, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Gerlag
authors.affiliation: Department of Rheumatology, St Vincent's University Hospital, Elm Park, Dublin, Ireland.
authors.forename: Eliza
authors.initials: E
authors.lastname: Pontifex
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.|Department of Rheumatology, St Vincent's University Hospital, Elm Park, Dublin, Ireland.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Veale
authors.affiliation: Department of Clinical Immunology and Rheumatology, F4-105, Academic Medical Centre/University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.|Department of Rheumatology, St Vincent's University Hospital, Elm Park, Dublin, Ireland.
authors.forename: Oliver
authors.initials: O
authors.lastname: FitzGerald
authors.affiliation: School of Medicine and Medical Science, UCD Conway Institute, University College Dublin, Belfield, Dublin, Ireland.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Pennington
mesh_terms: D000068879:Adalimumab / Q000627:therapeutic use*; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D015535:Arthritis, Psoriatic / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D000068800:Etanercept / Q000627:therapeutic use*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D020543:Proteome / Q000235:genetics / Q000276:immunology*; D013583:Synovial Membrane / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D018501:Antirheumatic Agents; D054316:Biomarkers, Pharmacological; D020543:Proteome; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab; D000068800:Etanercept
keywords: Anti-TNF-α; Biomarkers; Proteomics; Psoriatic arthritis; Synovium