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LILLA SOÓS, ZOLTÁN SZEKANECZ, ZOLTÁN SZABÓ, ANDREA FEKETE, MARGIT ZEHER, ILDIKÓ F. HORVÁTH, KATALIN DANKÓ, ANIKÓ KAPITÁNY, ANIKÓ VÉGVÁRI, SANDOR SIPKA, GYULA SZEGEDI, and GABRIELLA LAKOS

ABSTRACT.

Objective. Anti-cyclic citrullinated peptide (CCP) antibodies have emerged as sensitive and specific serological markers of rheumatoid arthritis (RA). However, antibodies to several other citrulline-containing proteins, including citrullinated fibrin and vimentin, have been detected in patients with RA, suggesting that citrulline is an essential constituent of autoantigens for RA-specific autoantibodies. We examined the diagnostic performance of the newly developed anti-mutated citrullinated vimentin (MCV) antibody assay.

Methods. Concentrations of anti-MCV, anti-CCP2, and rheumatoid factors (RF) were determined in the sera of 237 individuals: 119 patients with RA and 118 controls, including patients with other rheumatic diseases and healthy subjects. Diagnostic properties were compared by receiver-operating characteristic curve analysis.

Results. Using manufacturer's recommended cutoff values, sensitivity and specificity of anti-MCV antibodies were 75.6% and 91.5% in RA, compared to 66.4% and 98.3% for anti-CCP2. Introducing cutoff values to obtain the same 95% specificity resulted in decreased sensitivity of the anti-MCV test (69.7%) and increased sensitivity of the anti-CCP2 test (74.8%). At optimal cutoff levels, 29.4% of IgM RF-negative cases as well as 13.3% of anti-CCP2-negative cases in the RA group were anti-MCV-positive. Double-positivity for anti-MCV and anti-CCP2 provided 98.3% specificity with 97.5% positive predictive value in RA.

Conclusion. Overall, the performance of the novel anti-MCV ELISA for the diagnosis of RA is similar to that of the anti-CCP2 test [area under the curve 0.853 (95% CI 0.801–0.905) vs 0.910 (95% CI 0.873–0.946); p not significant]. As the diagnostic spectrum of the anti-MCV assay is somewhat different from that of anti-CCP2, the combined application of the 2 assays can improve the laboratory diagnostics of RA. (First Release July 1 2007; J Rheumatol 2007;34:1658-63)

Key Indexing Terms:

RHEUMATOID ARTHRITIS
ANTI-MUTATED CITRULLINATED VIMENTIN
ANTI-CYCLIC CITRULLINATED PEPTIDE 2
RHEUMATOID FACTOR

From the Division of Rheumatology, Laboratory of Immunology, and Division of Clinical Immunology, 3rd Department of Medicine, University of Debrecen, Medical and Health Science Center; and Research Group of Autoimmune Diseases, Hungarian Academy of Sciences, Debrecen, Hungary.

Supported by grant No. T048541 from the Hungarian National Scientific Research Fund (OTKA) (to ZS); and a Research Grant from the Hungarian Academy of Sciences (to GS).

Dr. Soós and Dr. Szekanecz contributed equally to this report.

L. Soós, MD; Z. Szekanecz, MD, DSc; Z. Szabó, MD; A. Végvári, MD, Division of Rheumatology; A. Fekete, MSc; A. Kapitány, PhD; S. Sipka, MD, DSc; G. Lakos, MD, PhD, Laboratory of Immunology; M. Zeher, MD, DSc; I.F. Horváth, MD; K. Dankó, MD, PhD, Division of Clinical Immunology, 3rd Department of Medicine, University of Debrecen; G. Szegedi, MD, DSc, Research Group of Autoimmune Diseases, Hungarian Academy of Sciences.

Address reprint requests to Dr. Z. Szekanecz, Division of Rheumatology, 3rd Department of Medicine, University of Debrecen, Medical and Health Science Center, 22 Moricz Street, Debrecen, H-4032, Hungary. E-mail: szekanecz@iiibel.dote.hu

Accepted for publication April 12, 2007.