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Diagnostic Utility of Anti-Cyclic Citrullinated Peptide Antibodies for Very Early Rheumatoid Arthritis

TOSHIHIRO MATSUI, KOTA SHIMADA, NAOKO OZAWA, HIROMI HAYAKAWA, FUTOSHI HAGIWARA, HISANORI NAKAYAMA, SHOJI SUGII, YOSHINORI OZAWA, and SHIGETO TOHMA

ABSTRACT.

Objective. To compare the diagnostic utility of anti-cyclic citrullinated peptide (anti-CCP) antibodies with other serological markers including rheumatoid factor (RF), anti-agalactosyl immunoglobulin G (IgG) antibody, and matrix metalloproteinase (MMP)-3 in very early rheumatoid arthritis (RA).

Methods. Serum concentrations of anti-CCP antibodies, RF, anti-agalactosyl IgG antibody, and MMP-3 were measured in 262 patients with RA ("total RA") including 55 patients with disease duration of less than 6 months who had not been treated before entry ("very early RA") and 116 patients with rheumatic diseases other than RA.

Results. The diagnostic sensitivity of anti-CCP antibodies was 82.4% in total RA and 67.3% in very early RA and was lower than that of RF (84.0% total RA, 83.6% very early RA) and anti-agalactosyl IgG antibody (90.5%, 90.9%), whereas specificity, positive predictive value, and diagnostic accuracy were the best among markers tested both in total RA and in very early RA. The presence of either anti-CCP antibodies or RF increased the sensitivity, but any combination of serological markers was not significantly better in diagnostic accuracy than anti-CCP antibodies alone. The rates of RF-positive subjects in anti-CCP antibody-negative patients both in total RA (43.5%) and in very early RA (61.1%) were higher than those of anti-CCP antibody-positive subjects in RF-negative patients (38.1% and 22.2%, for total RA and early RA, respectively).

Conclusion. Measurement of anti-CCP antibodies, by itself, is useful for the diagnosis of RA; however, combined use of anti-CCP antibodies with RF may be more useful than either method alone for the diagnosis of very early RA. (First Release Aug 15 2006; J Rheumatol 2006;33:2390-7)

Key Indexing Terms:

ANTI-CYCLIC CITRULLINATED PEPTIDE ANTIBODY
RHEUMATOID ARTHRITIS
ANTI-AGALACTOSYL IgG ANTIBODY
RHEUMATOID FACTOR


From the Department of Rheumatology; Division of Rheumatology, Clinical Research Center for Allergy and Rheumatology; and the Department of Rehabilitation, Sagamihara National Hospital, National Hospital Organization, Kanagawa, Japan.

Supported in part by grants from the Ministry of Health, Labour and Welfare, Japan; the National Hospital Organization; and the Manabe Foundation.

T. Matsui, MD, PhD, Staff Doctor; H. Nakayama, MD, Staff Doctor; Y. Ozawa, MD, Staff Doctor, Department of Rheumatology; K. Shimada, MD, PhD, Research Resident; N. Ozawa, Research Assistant; H. Hayakawa, Research Assistant; F. Hagiwara, MD, Research Associate; S. Tohma, MD, Department Head, Division of Rheumatology, Clinical Research Center for Allergy and Rheumatology; S. Sugii, MD, Staff Doctor, Department of Rehabilitation, Sagamihara National Hospital.

Address reprint requests to Dr. T. Matsui, Department of Rheumatology, Sagamihara National Hospital, National Hospital Organization, 18-1, Sakuradai Sagamihara-City, Kanagawa, 228-8522, Japan. E-mail: t-matsui@sagamihara-hosp.gr.jp

Accepted for publication May 6, 2006.




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