Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


Novel Multiplex Technology for Diagnostic Characterization of Rheumatoid Arthritis.

Chandra4,  Piyanka E., Sokolove3,  Jeremy, Hipp1,  Berthold G., Eberl1,  Heike, Klause1,  Ursula, Robinson2,  William

Roche Diagnostics
Stanford Univ School of Med, Stanford, CA
Stanford University, Mountain View, CA
Stanford University

Purpose:

To develop a clinical-grade, automated, multiplex system for the 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 bead-based commercial assay to measure cytokine levels, and developed an array-based assay using a novel multiplex technology research platform (Immunological Multi-Parameter Chip Technology) to evaluate autoantibody reactivities and bone-turnover markers. Positive values were defined as 2 standard deviations above that of healthy controls. Data were analyzed by Significance Analysis of Microarrays and hierarchical clustering software. Prediction rules were generated

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. Multiplex measurement of a subset of the differentiating biomarkers provided high sensitivity and specificity for the diagnostic discrimination of RA. Identification of distinct biomarker signatures enabled molecular stratification of early-stage RA into clinically relevant subtypes.

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.

Table 1. Performance characteristics of multiplex-assay autoantibody profiles in the diagnosis of rheumatoid arthritis.

Biomarker panelPPVNPVSensitivitySpecificity
1+ markers79.5%92.6%96.7%62.5%
2+ markers91.8%89.7%93.3%87.5%
3+ markers95.3%79.8%84.2%93.8%
4+ markers95.9%61.1%59.2%96.3%
Biomarker panel includes: Histone 2B/e (1–20), Vimentin (58–77) (Cit 64, 69, 71), FibrinogenA (616–635) (Cit 621, 627, 630), COMP (453–472), Profilaggrin (293–310) {Cit 301, 305}, RF-IgA.

To cite this abstract, please use the following information:
Chandra, Piyanka E., Sokolove, Jeremy, Hipp, Berthold G., Eberl, Heike, Klause, Ursula, Robinson, William; Novel Multiplex Technology for Diagnostic Characterization of Rheumatoid Arthritis. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1764
DOI: 10.1002/art.29529

Abstract Supplement

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