Developing clinically relevant biomarkers in inflammatory arthritis: A multiplatform approach for serum candidate protein discovery

Proteomics Clin Appl. 2016 Jun;10(6):691-8. doi: 10.1002/prca.201500046. Epub 2015 Nov 9.

Abstract

Purpose: To identify candidate biomarkers that have the potential to distinguish between patients with psoriatic arthritis (PsA) or rheumatoid arthritis (RA) and explore the value of combining different protein discovery platforms for the development of a multiplexed protein biomarker panel.

Experimental design: Serum samples from 32 patients (PsA; n = 16 and RA; n = 16) defined as active, early onset, and treatment naïve were analyzed using unbiased label-free LC-MS/MS, a microsphere bead-based immunoassay (Luminex xMAP) and an aptamer-based assay (SOMAscan).

Results: LC-MS/MS was used to quantify 324 proteins, while the Luminex xMAP targeted 48 proteins and SOMAscan supported the measurement of 1129 proteins. The combined data from these techniques gave reproducible quantification of 1501 proteins in total. Of these, 42 (LC-MS/MS), 3 (Luminex xMAP), and 127 (SOMAscan) proteins were found to be differentially expressed between PsA and RA (p < 0.05).

Conclusion and clinical relevance: Using three different and potentially complementary proteomic platforms we identified a total of 172 proteins that are differentially expressed in patients with PsA compared to RA. These proteins collectively represent candidates for inclusion in a protein signature that could be developed as a diagnostic test to discriminate patients with PsA from RA and therefore be of clinical utility.

Keywords: LC-MS/MS; Luminex; Multiplexing; Psoriatic and Rhuematoid Arthritis; SOMAscan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arthritis, Psoriatic / blood
  • Arthritis, Psoriatic / diagnosis*
  • Arthritis, Psoriatic / pathology
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / diagnosis*
  • Arthritis, Rheumatoid / pathology
  • Biomarkers / metabolism
  • Blood Proteins / metabolism*
  • Chromatography, Liquid
  • Diagnosis, Differential
  • Female
  • Gene Expression
  • Gene Expression Profiling
  • Humans
  • Immunoassay
  • Male
  • Middle Aged
  • Tandem Mass Spectrometry

Substances

  • Biomarkers
  • Blood Proteins