ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 909

Diagnostic Autoantibody Signatures Of Rheumatoid Arthritis Patients Identified With a Bead-Based Assay Approach

Angelika Lueking1, Petra Budde1, Stefan Vordenbäumen2, Carmen Theek1, Heike Goehler1, Martin Gamer1, Peter Schulz-Knappe1 and Matthias Schneider3, 1Protagen AG, Dortmund, Germany, 2Department of Rheumatology, Univ. Duesseldorf, Düsseldorf, Germany, 3Rheumatology, Heinrich-Heine-University, Düsseldorf, Germany

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: B cells in Human and Animal Arthritis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Rheumatoid arthritis (RA) is an autoimmune disease typically characterized by chronic inflammation, accumulation of self-reactive B-cells and production of autoantibodies of which anti–cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) have diagnostic utility. 30% of RA patients remain sero-negative making the early diagnosis of RA more difficult. Our goal is to develop a novel autoantibody-based diagnostic test that allows to correctly diagnosing CCP-negative early RA patients.

Methods: We performed a large-scale screen of 5800 proteins in a total of 250 serum samples of patients with stable RA, patients with SLE and healthy volunteers. An automated bead-based Luminex xMAP technology enables to measure the reactivity of autoantibodies to up to 500 different antigens in one single serum sample. All proteins are produced from E.coli, are highly purified by affinity capturing, sequenced by mass spectrometry, and each protein is coupled in optimized concentration to individual color coded Luminex beads. Biostatistical analysis was performed using univariate as well as multivariate statistical algorithms.

Results: 144 novel antigens were identified in RA patients. The autoantibody profile of RA patients is heterogeneous with some overlap between CCP-positive and CCP-negative patients. We therefore evaluated panels comprising five to ten antigens for identification of CCP-negative RA patients. One panel with six antigens showed a specificity comparable to CCP in CCP-negative patients. Another panel was able to detect about 60% of CCP-negative. Comparison to an active control group consisting of 100 SLE patients, an AUC was obtained of 0.78, with high a specificity of 0.86 and a lower sensitivity of 0.54.

Conclusion: CCP-negative RA patients can be identified based on specific set of autoantibodies. Further studies are currently conducted to validate the biomarker panels in early RA patients.

Disclosure:

A. Lueking,

Protagen ,

3;

P. Budde,

Protagen,

3;

S. Vordenbäumen,
None;

C. Theek,

Protagen,

3;

H. Goehler,

Protagen,

3;

M. Gamer,

Protagen,

3;

P. Schulz-Knappe,

Protagen,

6;

M. Schneider,
None.

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