Session Information
Title: Rheumatoid Arthritis - Clinical Aspects: Novel Biomarkers and Other Measurements of Disease Activity
Session Type: Abstract Submissions (ACR)
Background/Purpose:
Autoantibodies (auto-Ab) against citrullinated peptides (ACPA) and rheumatoid factor (RF) are important biomarkers in the diagnostic process of rheumatoid arthritis (RA). However, RF or ACPA are undetectable in up to 30% of RA patients who can be referred to as „seronegative“. In these cases, the diagnosis is often challenging. Early diagnosis in turn is important for improved outcome. In search for an optimized serologic diagnostic strategy, a comprehensive auto-Ab screening was performed in RA patients.
Methods:
5,892 recombinant human antigens were covalently coupled to fluorescent beads, incubated with patients‘ sera and detected by a secondary, fluorescent antibody using Luminex xMAP technology. In an explorative phase, auto-Ab profiles were compared between 72 established RA patients according to ACR/EULAR criteria, 71 matched healthy controls, and 129 systemic lupus erythematosus (SLE) patients in an age- and gender-adjusted manner. Predefined multi- and univariate analyses were employed to generate a diagnostic panel of auto-Ab for further testing. In a validation phase, the diagnostic potential of this panel was assessed in 116 RA patients from a randomized controlled trial (HIT-HARD) against 116 matched healthy controls employing logistic regression modelling.
Results
A panel of 11 auto-Ab (including ACPA) showed the best diagnostic properties and was further assessed. In the explorative phase sensitivity/specificity/area under the curve (AUC) were 0.9/0.9/0.97 for RA patients against healthy controls and 0.79/0.92/0.93 against SLE. Omitting ACPA resulted in slightly weaker test performance with sensitivity/specificity/AUC of 0.9/0.86/0.95. When only seronegative (ACPA and RF negative) patients were considered, sensitivity/specificity/AUC was 1.0/1.0/1.0 against healthy controls. In the validation phase on early RA patients from the HIT-HARD study, the panel showed sensitivity/specificity/AUC of 0.71/0.53/0.68 with ACPA and only slightly weaker performance at 0.71/0.52/0.67 without ACPA. Seronegative patients were detected with sensitivity/specificity/AUC of 0.09/0.96/0.78.
Conclusion
The multiplex bead-based approach showed promising results concerning the identification of potential diagnostic markers for seronegative RA. The need for rigorous validation of such explorative approaches to control for over-fitting is clearly demonstrated. Future improvements of the technology such as citrullination of recombinant antigens may further enhance detectability of “seronegative” patients.
Disclosure:
S. Vordenbäumen,
None;
A. Lueking,
Protagen AG,
3;
C. Theek,
Protagen AG,
3;
R. Brinks,
GlaxoSmithKline,
9,
UCB,
9;
R. Fischer-Betz,
None;
J. Richter,
GlaxoSmithKline,
9,
UCB,
9;
E. Bleck,
None;
J. Detert,
None;
G. Burmester,
AbbVie, Pfizer, UCB, Roche,
2,
AbbVie, BMS, Pfizer, Merck, MedImmune, UCB, Roche,
5,
AbbVie, BMS, Pfizer, Merck, UCB, Roche,
8;
P. Schulz-Knappe,
Protagen AG,
3;
M. Schneider,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/development-and-validation-of-a-diagnostic-bead-based-multiplex-autoantibody-assayscreening-for-autoantibodies-to-detect-seronegative-rheumatoid-arthritis/