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

ES Collins, AQ Butt, DS Gibson, M Dunn, U Fearon, AW van Kuijk, DM Gerlag, E Pontifex, DJ Veale, PP Tak, O Fitzgerald, SR Pennington

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to) 645-662
Number of pages18
JournalPROTEOMICS - Clinical Applications
Volume10
Issue number6
Early online date28 Sep 2015
DOIs
Publication statusPublished - 1 Jun 2016

Keywords

  • Psoriatic arthritis
  • anti-TNF-α
  • biomarkers
  • synovium
  • proteomics

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