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IgG Oligosaccharide Alterations Are a Novel Diagnostic Marker for Disease Activity and the Clinical Course of Inflammatory Bowel Disease

Shinzaki, Shinichiro, M.D.1; Iijima, Hideki, M.D., Ph.D.1; Nakagawa, Takatoshi, Ph.D.2; Egawa, Satoshi, M.D.1; Nakajima, Sachiko, M.D.1; Ishii, Shuji, M.D.1; Irie, Takanobu, M.D., Ph.D.1; Kakiuchi, Yoshimi, M.D., Ph.D.1; Nishida, Tsutomu, M.D., Ph.D.1; Yasumaru, Masakazu, M.D., Ph.D.1; Kanto, Tatsuya, M.D., Ph.D.3; Tsujii, Masahiko, M.D., Ph.D.1; Tsuji, Shingo, M.D., Ph.D.1; Mizushima, Tsunekazu, M.D., Ph.D.6; Yoshihara, Harumasa, M.D., Ph.D.5; Kondo, Akihiro, Ph.D.2; Miyoshi, Eiji, M.D., Ph.D.4; Hayashi, Norio, M.D., Ph.D.1

American Journal of Gastroenterology: May 2008 - Volume 103 - Issue 5 - p 1173–1181
ORIGINAL CONTRIBUTION: INFLAMMATORY BOWEL DISEASE
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BACKGROUND AND AIMS Patients with inflammatory bowel disease (IBD) share several immunologic similarities with rheumatoid arthritis (RA). Patients with RA have significantly increased levels of serum agalactosyl immunoglobulin G (IgG). Our aim was to investigate the clinical significance of analyzing the oligosaccharide structure of serum IgG in patients with IBD.

METHODS Serum IgG oligosaccharide structures were analyzed using high-performance liquid chromatography in 60 patients with Crohn's disease (CD), 58 patients with ulcerative colitis (UC), 27 healthy volunteers (HV), and 15 disease controls (DC). The activity and mRNA level of beta-1,4-galactosyltransferase (Beta4GalT) in antibody-secreting cells were investigated in these subjects.

RESULTS The agalactosyl fraction of the fucosylated IgG oligosaccharides (G0F/G2F) in CD and UC was significantly greater than that in HV and DC (P < 0.001). The percentage of subjects with a high G0F/G2F in CD, UC, HV, and DC was 72%, 33%, 0%, and 0%, respectively. G0F/G2F, which is significantly correlated with disease severity in both CD and UC, had higher sensitivity to diagnose IBD compared with anti-Saccharomyces cerevisiae antibody. Moreover, G0F/G2F was significantly correlated with the prognosis of UC patients: patients with a high G0F/G2F did not maintain long-term remission. The activity and mRNA level of Beta4GalT were significantly elevated in UC but not in CD.

CONCLUSIONS G0F/G2F is a potentially effective diagnostic marker of disease activity in both CD and UC, and of the clinical course in UC. A pathophysiologic difference between CD and UC was also demonstrated.

1Department of Gastroenterology and Hepatology, 2Department of Glycotherapeutics, 3Department of Dendritic Cell Biology and Clinical Application, and 4Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; 5Department of Gastroenterology, Osaka Rosai Hospital, Sakai, Osaka, Japan; and 6Department of Surgery, Rinku General Medical Center, Izumisano Municipal Hospital, Izumisano, Osaka, Japan

Reprint requests and correspondence: Hideki Iijima, M.D., Ph.D., Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2–2 K1 Yamadaoka, Suita, Osaka 565–0871, Japan.

Received August 6, 2007; accepted November 5, 2007.

© The American College of Gastroenterology 2008. All Rights Reserved.
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