title: Functional analysis of agalactosyl IgG in inflammatory bowel disease patients.
abstract: 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.
authors.affiliation: Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Nakajima
authors.forename: Hideki
authors.initials: H
authors.lastname: Iijima
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Shinzaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Egawa
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inoue
authors.forename: Akira
authors.initials: A
authors.lastname: Mukai
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Jumpei
authors.initials: J
authors.lastname: Kondo
authors.forename: Tomofumi
authors.initials: T
authors.lastname: Akasaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nishida
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kanto
authors.forename: Eiichi
authors.initials: E
authors.lastname: Morii
authors.forename: Tsunekazu
authors.initials: T
authors.lastname: Mizushima
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Tsujii
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000378:metabolism*; D003424:Crohn Disease / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins / Q000097:blood / Q000235:genetics; D010587:Phagocytosis; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012756:Sheep; D014157:Transcription Factors / Q000097:blood / Q000235:genetics
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007074:Immunoglobulin G; C499048:MBP protein, human; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; C064155:agalactosyl IGG