ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1207

Design of a Multiplex Serum Proteome Assay to Monitor Biologic Drug Response in Rheumatoid Arthritis Patients

Niamh Callan1, Aisha Butt1, Stephen R. Pennington2, Cathy McGeough3, Philip Gardiner4, Gary Wright5, Tony Bjourson3 and David S. Gibson6, 1Proteome Research Centre, Conway Institute, University College Dublin, Dublin, Ireland, 2Proteome Research Centre, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland, 3Northern Ireland Centre for Stratified Medicine, Ulster University, Londonderry, United Kingdom, 4Rheumatology, Altnagelvin Hospital, Londonderry, United Kingdom, 5Rheumatology, Musgrave Park Hospital, BELFAST, United Kingdom, 6Inflammatory Disease Research Group, Northern ireland Centre for Stratified Medicine, Ulster University, Londonderry, United Kingdom

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , , , ,

Session Information

Date: Monday, November 14, 2016

Title: Genetics, Genomics and Proteomics - Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Biologic drugs have revolutionised the treatment of Rheumatoid Arthritis (RA), however these therapies are expensive and exhibit a high non–response rate (30%). Currently there are no specific biological markers which distinguish non-response early after initiating treatment. The aim of this study was to identify serum protein levels which change when disease activity score is reduced by biologic drug treatment. These proteins may give mechanistic insight into molecular events after failed therapeutic intervention.

Methods: Sera and disease activity scores (DAS28-ESR) were collected from n=25 RA patients at baseline and six months after anti-tumour necrosis factor alpha treatment. EULAR response criteria were used. Untargeted (unbiased) label free LC-MS/MS based proteomics was used initially to discover sera proteins differentially expressed at six months in responders and non-responders. Multiple reaction monitoring (MRM) assays were designed and tested on a triple quadrupole mass spectrometer.

Results: Over 500 proteins were identified in each of the pooled serum samples using the untargeted label free LC-MS/MS approach. Statistical analysis of the data revealed a list of 155 proteins that were significantly differentially expressed between good and non-responders (p<0.05). 55 of these proteins were shortlisted for development of targeted MRM assays, and assays were successfully developed for 47 proteins.

Conclusion: The approach outlined here and the initial results obtained indicate the power of a combined mass spectrometry strategy for comprehensive serum proteome analysis to determine quantitative changes, discover novel protein signatures and develop a multiplexed protein assay capable of monitoring response to biologic treatments. Such biologic drug response markers could minimise the use of expensive biologic drugs in patients who do not gain benefit and reduce adverse side effects.

Disclosure: N. Callan, None; A. Butt, None; S. R. Pennington, None; C. McGeough, None; P. Gardiner, None; G. Wright, None; T. Bjourson, None; D. S. Gibson, None.

To cite this abstract in AMA style:

Callan N, Butt A, Pennington SR, McGeough C, Gardiner P, Wright G, Bjourson T, Gibson DS. Design of a Multiplex Serum Proteome Assay to Monitor Biologic Drug Response in Rheumatoid Arthritis Patients [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/design-of-a-multiplex-serum-proteome-assay-to-monitor-biologic-drug-response-in-rheumatoid-arthritis-patients/. Accessed .

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