Original Contribution
The American Journal of Gastroenterology (2008) 103, 1173–1181; doi:10.1111/j.1572-0241.2007.01699.x
IgG Oligosaccharide Alterations Are a Novel Diagnostic Marker for Disease Activity and the Clinical Course of Inflammatory Bowel Disease
Shinichiro Shinzaki MD1, Hideki Iijima MD, PhD1, Takatoshi Nakagawa PhD2, Satoshi Egawa MD1, Sachiko Nakajima MD1, Shuji Ishii MD1, Takanobu Irie MD, PhD1, Yoshimi Kakiuchi MD, PhD1, Tsutomu Nishida MD, PhD1, Masakazu Yasumaru MD, PhD1, Tatsuya Kanto MD, PhD3, Masahiko Tsujii MD, PhD1, Shingo Tsuji MD, PhD1, Tsunekazu Mizushima MD, PhD6, Harumasa Yoshihara MD, PhD5, Akihiro Kondo PhD2, Eiji Miyoshi MD, PhD4 and Norio Hayashi MD, PhD1
- 1Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- 2Department of Glycotherapeutics, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- 3Department of Dendritic Cell Biology and Clinical Application, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
- 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
- 6Department of Surgery, Rinku General Medical Center, Izumisano Municipal Hospital, Izumisano, Osaka, Japan
Correspondence: Hideki Iijima, MD, PhD, Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Received 6 August 2007; Accepted 5 November 2007.
Abstract
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.
