Functional analysis of agalactosyl IgG in inflammatory bowel disease patients
Sachiko Nakajima MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
The first two authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
Hideki Iijima MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
The first two authors contributed equally to this work.
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka 565-0871, JapanSearch for more papers by this authorShinichiro Shinzaki MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorSatoshi Egawa MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorTakahiro Inoue MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorAkira Mukai MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorYoshito Hayashi MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorJumpei Kondo MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorTomofumi Akasaka MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorTsutomu Nishida MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorTatsuya Kanto MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Department of Dendritic Cell Biology and Clinical Application, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorEiichi Morii MD, PhD
Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorTsunekazu Mizushima MD, PhD
Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorEiji Miyoshi MD, PhD
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorMasahiko Tsujii MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorNorio Hayashi MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorSachiko Nakajima MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
The first two authors contributed equally to this work.
Search for more papers by this authorCorresponding Author
Hideki Iijima MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
The first two authors contributed equally to this work.
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, 2-2 K1 Yamadaoka, Suita, Osaka 565-0871, JapanSearch for more papers by this authorShinichiro Shinzaki MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorSatoshi Egawa MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorTakahiro Inoue MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorAkira Mukai MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorYoshito Hayashi MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorJumpei Kondo MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorTomofumi Akasaka MD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorTsutomu Nishida MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorTatsuya Kanto MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Department of Dendritic Cell Biology and Clinical Application, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorEiichi Morii MD, PhD
Department of Pathology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorTsunekazu Mizushima MD, PhD
Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorEiji Miyoshi MD, PhD
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorMasahiko Tsujii MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorNorio Hayashi MD, PhD
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan
Search for more papers by this authorAbstract
Background:
Agalactosyl immunoglobulin (Ig) G is increased in inflammatory bowel disease (IBD) similarly to rheumatoid arthritis (RA). The lectin complement pathway is shown to be activated through association of agalactosyl IgG with mannan-binding lectin (MBL) in RA. Functional changes of IgG agalactosylation in IBD, however, have not yet been clarified.
Methods:
The ratio of the agalactosyl/non-agalactosyl fraction in fucosylated IgG oligosaccharides (G0F/G2F) and serum MBL levels were analyzed in 59 patients with Crohn's disease (CD), 64 ulcerative colitis (UC), and 39 healthy volunteers (HV). The MBL levels associated with serum IgG were analyzed by enzyme-linked immunosorbent assay. MBL expression in the intestinal mucosa was analyzed by immunohistochemistry. Phagocytosis of sheep red blood cells (SRBC) reacted with either an agalactosyl or non-agalactosyl SRBC-specific IgG antibody was determined by flow cytometry.
Results:
The serum MBL levels were not significantly different among CD, UC, or HV. In patients with CD, the serum MBL levels were negatively correlated with the Crohn's Disease Activity Index (CDAI). The levels of MBL associated with agalactosyl IgG were not different from those associated with non-agalactosyl IgG. Immunoreactivity to MBL was less in the inflamed mucosa compared with the noninflamed mucosa. Phagocytic activity of SRBC was significantly higher in the presence of agalactosyl IgG compared to non-agalactosyl IgG.
Conclusions:
Agalactosyl IgG oligosaccharides enhanced antibody-dependent phagocytosis in vitro but did not activate the lectin complement pathway. Oligosaccharide alterations of IgG are not only a marker of IBD but also functionally modulate the immune function of IBD. (Inflamm Bowel Dis 2010;)
Supporting Information
Additional supporting information may be found in the online version of this article.
| Filename | Description |
|---|---|
| IBD_21459_sm_suppinfofigureS1.tif141 KB | The clinical utility of the MR-UC risk score is demonstrated by positive (A) and negative (B) likelihood ratios; sensitivity (C) and specificity (D); and positive (E) and negative (F) predictive values. A score of 44 (C) and 47 (D) can be used to generate a test with a sensitivity and specificity of over 90%, respectively. Recommended (see discussion) positive likelihood ratio parameter of >10 and negative likelihood ratio parameter of <0.1 are met with a score of 47 (A) and 43 (B), respectively. |
| IBD_21459_sm_suppinfotableS1.doc364.5 KB | Table S1: Top 100 associated SNPs from Analysis-I. |
| IBD_21459_sm_suppinfotableS2.doc198.5 KB | Table S2: Top 65 associated SNPs from Analysis-II. |
| IBD_21459_sm_suppinfotableS3.doc186.5 KB | Table S3: MHC region associated SNPs from Analysis-III. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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