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Open Access Highly Accessed Research article

Novel multiplex technology for diagnostic characterization of rheumatoid arthritis

Piyanka E Chandra12, Jeremy Sokolove12, Berthold G Hipp3, Tamsin M Lindstrom12, James T Elder4, John D Reveille5, Heike Eberl3, Ursula Klause3 and William H Robinson12*

Author Affiliations

1 Division of Immunology and Rheumatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA

2 Geriatric Research Education and Clinical Centers, Palo Alto VA Health Care System, 3801 Miranda Avenue, Palo Alto, CA 94304, USA

3 Roche Diagnostics GmbH, Nonnenwald 2, 82377 Penzberg, Germany

4 Department of Dermatology, University of Michigan, Ann Arbor, MI 48109, USA

5 Division of Rheumatology, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA

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Arthritis Research & Therapy 2011, 13:R102  doi:10.1186/ar3383

Published: 24 June 2011

Abstract

Introduction

The aim of this study was to develop a clinical-grade, automated, multiplex system for the differential diagnosis and molecular stratification of rheumatoid arthritis (RA).

Methods

We profiled autoantibodies, cytokines, and bone-turnover products in sera from 120 patients with a diagnosis of RA of < 6 months' duration, as well as in sera from 27 patients with ankylosing spondylitis, 28 patients with psoriatic arthritis, and 25 healthy individuals. We used a commercial bead assay to measure cytokine levels and developed an array assay based on novel multiplex technology (Immunological Multi-Parameter Chip Technology) to evaluate autoantibody reactivities and bone-turnover markers. Data were analyzed by Significance Analysis of Microarrays and hierarchical clustering software.

Results

We developed a highly reproducible, automated, multiplex biomarker assay that can reliably distinguish between RA patients and healthy individuals or patients with other inflammatory arthritides. Identification of distinct biomarker signatures enabled molecular stratification of early-stage RA into clinically relevant subtypes. In this initial study, multiplex measurement of a subset of the differentiating biomarkers provided high sensitivity and specificity in the diagnostic discrimination of RA: Use of 3 biomarkers yielded a sensitivity of 84.2% and a specificity of 93.8%, and use of 4 biomarkers a sensitivity of 59.2% and a specificity of 96.3%.

Conclusions

The multiplex biomarker assay described herein has the potential to diagnose RA with greater sensitivity and specificity than do current clinical tests. Its ability to stratify RA patients in an automated and reproducible manner paves the way for the development of assays that can guide RA therapy.