A Clinically Based Protein Discovery Strategy to Identify Potential Biomarkers of Response to Anti-TNF-alpha 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

6 Citations (Scopus)

Abstract

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
LanguageEnglish
Pages 645-662
Number of pages17
JournalProteomics - Clinical Applications
Volume10
Issue number6
DOIs
Publication statusPublished - 24 Jun 2015

Fingerprint

Psoriatic Arthritis
Tumor Necrosis Factor-alpha
Biomarkers
Proteins
Biological Products
Therapeutics
Gels
Interleukin-23
Biological Therapy
Interleukin-17
Interleukins
Proteomics
Arthritis
Electrophoresis

Keywords

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

Cite this

Collins, ES ; Butt, AQ ; Gibson, DS ; Dunn, M ; Fearon, U ; van Kuijk, AW ; Gerlag, DM ; Pontifex, E ; Veale, DJ ; Tak, PP ; Fitzgerald, O ; Pennington, SR. / A Clinically Based Protein Discovery Strategy to Identify Potential Biomarkers of Response to Anti-TNF-alpha Treatment of Psoriatic Arthritis. In: Proteomics - Clinical Applications. 2015 ; Vol. 10, No. 6. pp. 645-662.
@article{24264bdbbe1f4b1482050555b1a8a67f,
title = "A Clinically Based Protein Discovery Strategy to Identify Potential Biomarkers of Response to Anti-TNF-alpha Treatment of Psoriatic Arthritis",
abstract = "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",
keywords = "Psoriatic arthritis, anti-TNF-α, biomarkers, synovium, proteomics",
author = "ES Collins and AQ Butt and DS Gibson and M Dunn and U Fearon and {van Kuijk}, AW and DM Gerlag and E Pontifex and DJ Veale and PP Tak and O Fitzgerald and SR Pennington",
year = "2015",
month = "6",
day = "24",
doi = "10.1002/prca.201500051",
language = "English",
volume = "10",
pages = "645--662",
journal = "Proteomics - Clinical Applications",
issn = "1862-8346",
number = "6",

}

Collins, ES, Butt, AQ, Gibson, DS, Dunn, M, Fearon, U, van Kuijk, AW, Gerlag, DM, Pontifex, E, Veale, DJ, Tak, PP, Fitzgerald, O & 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, vol. 10, no. 6, pp. 645-662. https://doi.org/10.1002/prca.201500051

A Clinically Based Protein Discovery Strategy to Identify Potential Biomarkers of Response to Anti-TNF-alpha Treatment of Psoriatic Arthritis. / Collins, ES; Butt, AQ; Gibson, DS; Dunn, M; Fearon, U; van Kuijk, AW; Gerlag, DM; Pontifex, E; Veale, DJ; Tak, PP; Fitzgerald, O; Pennington, SR.

In: Proteomics - Clinical Applications, Vol. 10, No. 6, 24.06.2015, p. 645-662.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A Clinically Based Protein Discovery Strategy to Identify Potential Biomarkers of Response to Anti-TNF-alpha Treatment of Psoriatic Arthritis

AU - Collins, ES

AU - Butt, AQ

AU - Gibson, DS

AU - Dunn, M

AU - Fearon, U

AU - van Kuijk, AW

AU - Gerlag, DM

AU - Pontifex, E

AU - Veale, DJ

AU - Tak, PP

AU - Fitzgerald, O

AU - Pennington, SR

PY - 2015/6/24

Y1 - 2015/6/24

N2 - 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

AB - 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

KW - Psoriatic arthritis

KW - anti-TNF-α

KW - biomarkers

KW - synovium

KW - proteomics

U2 - 10.1002/prca.201500051

DO - 10.1002/prca.201500051

M3 - Article

VL - 10

SP - 645

EP - 662

JO - Proteomics - Clinical Applications

T2 - Proteomics - Clinical Applications

JF - Proteomics - Clinical Applications

SN - 1862-8346

IS - 6

ER -