Increased levels of galactose-deficient anti-Gal immunoglobulin G in the sera of hepatitis C virus-infected individuals with fibrosis and cirrhosis.
Hepatitis B and C viruses are major causative agents of liver fibrosis, cirrhosis, and liver cancer. Using comparative glycoproteomics, we identified a glycoprotein that is altered both in amount and in glycosylation as a function of liver fibrosis and cirrhosis. Specifically, this altered glycoprotein is an immunoglobulin G (IgG) molecule reactive to the heterophilic alpha-Gal epitope [Galalpha-1-3Galbeta1-(3)4GlcNAc-R]. While similar changes in glycosylation have been observed in several autoimmune diseases, the specific immunoglobulins and their antigen recognition profiles were not determined. Thus, we provide the first report identifying the specific antigenic recognition profile of an immunoglobulin molecule containing altered glycosylation as a function of liver disease. This change in glycosylation allowed increased reactivity with several fucose binding lectins and permitted the development of a plate-based assay to measure this change. Increased lectin reactivity was observed in 100% of the more than 200 individuals with stage III or greater fibrosis and appeared to be correlated with the degree of fibrosis. The reason for the alteration in the glycosylation of anti-Gal IgG is currently unclear but may be related to the natural history of the disease and may be useful in the noninvasive detection of fibrosis and cirrhosis.
Mehta
Anand S
AS
Drexel University College of Medicine and Department of Microbiology and Immunology and Drexel Institute for Biotechnology and Virology, Doylestown, PA 18901, USA. anand.mehta@drexel.edu
Long
Ronald E
RE
Comunale
Mary Ann
MA
Wang
Mengjun
M
Rodemich
Lucy
L
Krakover
Jonathan
J
Philip
Ramila
R
Marrero
Jorge A
JA
Dwek
Raymond A
RA
Block
Timothy M
TM
D000328:Adult; D016174:Hepacivirus; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D037102:Lectins / Q000378:metabolism; D008103:Liver Cirrhosis / Q000276:immunology*; D008875:Middle Aged; D014312:Trisaccharides / Q000276:immunology
D007074:Immunoglobulin G; D037102:Lectins; D014312:Trisaccharides; C076569:alpha-galactosyl epitope; C027112:fucose-binding lectin