ARTHRITIS & RHEUMATISM Vol. 58, No. 1, January 2008, pp 36–45 DOI 10.1002/art.23188 © 2008, American College of Rheumatology Antibodies Against Citrullinated Vimentin in Rheumatoid Arthritis Higher Sensitivity and Extended Prognostic Value Concerning Future Radiographic Progression as Compared With Antibodies Against Cyclic Citrullinated Peptides Linda Mathsson, 1 Mohammed Mullazehi, 1 Marius C. Wick, 2 Olof Sj¨ oberg, 1 Ronald van Vollenhoven, 3 Lars Klareskog, 3 and Johan R ¨ onnelid 4 Objective. The Sa autoantigen can be found in inflamed synovium of patients with rheumatoid arthri- tis (RA), and at least part of the humoral RA-specific anti-Sa response is directed against citrullinated vimen- tin. This study was undertaken to evaluate the sensitiv- ity, specificity, and prognostic value of determination of levels of antibodies against modified citrullinated vi- mentin (anti-MCV) as compared with antibodies against cyclic citrullinated peptides (anti-CCP) in an inception cohort of patients with early RA. Methods. Clinical data, radiographs, and measure- ments of levels of anti-MCV and anti-CCP antibodies were obtained in 273 patients with early RA at baseline, after 3 months, and after 1, 2, 3, and 5 years. Auto- antibodies were also analyzed in 100 healthy controls. Results. Of the 273 patients, 193 (70.7%) were anti-MCV positive and 158 (57.9%) were anti-CCP positive at the time of diagnosis, with nearly equal specificities (95% and 96%, respectively). Forty (14.7%) were anti-MCV positive only, and 5 (1.8%) were anti- CCP positive only. Anti-MCV–positive and anti-MCV– negative patients had similar disease activity at base- line, but presence of anti-MCV was predictive of subsequent high disease activity and continued radio- graphic progression. Changes in anti-MCV level showed stronger correlation with changes in clinical parameters than did changes in anti-CCP level. The subgroup of patients who were anti-MCV positive and anti-CCP negative showed a higher rate of radiographic destruc- tion than did patients who were negative for both anti-MCV and anti-CCP. Conclusion. These findings show that when pa- tients with early RA are compared with healthy controls, analysis of anti-MCV yields greater sensitivity and unchanged specificity as compared with analysis of anti-CCP. Anti-MCV also appears to perform better than anti-CCP in identifying poor radiographic progno- sis in patients with early RA. Several different autoantibodies with varying specificity have been found in serum from patients with RA (1,2), but rheumatoid factor (RF) is at present the only autoantibody included in the American College of Rheumatology (ACR) classification criteria (3). How- ever, antibodies recognizing citrullinated proteins/ peptides (4), especially the peptide mixture designated cyclic citrullinated peptides (CCP) (5), have reasonable sensitivity and high specificity for RA and are increas- Supported by grants from the Swedish Fund for Research Without Animal Experiments, the Agnes and Mac Rudberg Founda- tion, King Gustav V’s 80-Year Fund, Signe and Reinhold Sund’s Foundation for Rheumatological Research, and the Swedish Rheuma- tism Association. Orgentec Inc. supplied anti-MCV kits for the study. 1 Linda Mathsson, MSc, Mohammed Mullazehi, MSc, Olof Sjo ¨berg, MD, PhD: Uppsala University, Uppsala, Sweden; 2 Marius C. Wick, MD: Karolinska Institute, Stockholm, Sweden, and Innsbruck Medical University, Innsbruck, Austria; 3 Ronald van Vollenhoven, MD, PhD, Lars Klareskog, MD, PhD: Karolinska Institute, Stockholm, Sweden; 4 Johan Ro ¨nnelid, MD, PhD: Uppsala University, Uppsala, Sweden, and Karolinska Institute, Stockholm, Sweden. Dr. Klareskog has received consulting fees, speaking fees, and/or honoraria (less than $10,000 each) from Wyeth, Schering- Plough, Bristol-Myers Squibb, Abbott, Roche, and Amgen. Dr. Ro ¨n- nelid has received speaking fees (less than $10,000 each) from Schering-Plough, Wyeth, Pfizer, and Roche. Address correspondence and reprint requests to Johan Ro ¨n- nelid, MD, PhD, Unit of Clinical Immunology, Rudbeck Laboratory C5, Uppsala University, SE-751 85 Uppsala, Sweden. E-mail: johan.ronnelid@klinimm.uu.se. Submitted for publication November 26, 2006; accepted in revised form September 7, 2007. 36