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.