Functional analysis of agalactosyl IgG in inflammatory bowel disease patients.
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.
Nakajima
Sachiko
S
Department of Gastroenterology and Hepatology, Osaka University Graduate School of Medicine, Osaka, Japan.
Iijima
Hideki
H
Shinzaki
Shinichiro
S
Egawa
Satoshi
S
Inoue
Takahiro
T
Mukai
Akira
A
Hayashi
Yoshito
Y
Kondo
Jumpei
J
Akasaka
Tomofumi
T
Nishida
Tsutomu
T
Kanto
Tatsuya
T
Morii
Eiichi
E
Mizushima
Tsunekazu
T
Miyoshi
Eiji
E
Tsujii
Masahiko
M
Hayashi
Norio
N
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
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