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.


A Novel Diagnostic Marker for RA, Anti-MCV.

Zablocki1,  Rong W., Van der Helm-van Mil3,  Annette, Huizinga3,  Tom, Rao2,  Srinivas

Cypress Bioscience Inc, San Diego, CA
Cypress Bioscience Inc
Leiden University Medical Center, The Netherlands

Purpose:

Early identification of undifferentiated arthritis (UA) patients at greatest risk for developing rheumatoid arthritis (RA) may facilitate better treatment. Rheumatoid factor (RF IgM) and antibodies against cyclic citrullinated peptide (anti-CCP) are widely used in diagnosing RA. It has been suggested that the enzyme-linked immunosorbent assay (ELISA) to detect mutated, citrullinated vimentin (anti-MCV) may have a different diagnostic spectrum versus anti-CCP. The purpose of the current study was to evaluate the diagnostic performance of combinations of these biomarkers in UA-RA patients.

Methods:

Clinical and laboratory data were analyzed from a 470 patient subset of the previously described 570 patient Leiden Early Arthritic Clinic cohort (A. Van der Helm-van Mil, et al., 2007). These patients presented with UA, and a fraction (n=153) progressed to RA within 1 year, based on the fulfillment of the American College of Rheumatology (ACR) criteria. Anti-MCV, Anti-CCP2 and RF IgM tests were performed. A positive result for a combination was defined as resulting when all constituents were positive; a negative result of any constituent was defined as the combination negative. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), as well as their 95% confidence intervals (CI), were calculated for each individual biomarker as well as their combinations.

Results:

Table 1 presented the diagnostic performance of the biomarkers and their combinations. Overall, anti-MCV demonstrated the highest sensitivity (63%) and NPV (82%), though at the cost of reduced PPV (60%). Combining Anti-CCP2 and Anti-MCV barely reduced sensitivity comparing to Anti-CCP2 alone (52% vs. 53%), and exhibited a favorable balance in sensitivity/specificity and in PPV/NPV. Further, the sensitivity diagram (at right) revealed that anti-CCP2 did not provide additional information (sensitivity=0%) in the context of both RF IgM and anti-MCV being positive. However, anti-MCV and RF IgM still respectively retained 10% and 5% sensitivity despite positivity of the other 2 assays.

Conclusions:

Anti-MCV showed the highest sensitivity and NPV. Nearly all Anti-CCP2 positive RA patients were also Anti-MCV positive, though not vice versa, reinforcing the notion that the diagnostic spectrum of the 2 assays is not identical. In the context of positive results for both anti-MCV and RF IgM, anti-CCP2 became redundant in term of sensitivity. In summary, incorporating anti-MCV as an adjunctive diagnostic tool to prognosticate future RA in patients who present with UA enhances sensitivity.

To cite this abstract, please use the following information:
Zablocki, Rong W., Van der Helm-van Mil, Annette, Huizinga, Tom, Rao, Srinivas; A Novel Diagnostic Marker for RA, Anti-MCV. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :660
DOI: 10.1002/art.28428

Abstract Supplement

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