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Journal of Virology, February 2008, p. 1259-1270, Vol. 82, No. 3
0022-538X/08/$08.00+0     doi:10.1128/JVI.01600-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Increased Levels of Galactose-Deficient Anti-Gal Immunoglobulin G in the Sera of Hepatitis C Virus-Infected Individuals with Fibrosis and Cirrhosis

Drexel University College of Medicine and Department of Microbiology and Immunology and Drexel Institute for Biotechnology and Virology, 700 East Butler Avenue, Doylestown, Pennsylvania 18901,¹ Institute for Hepatitis and Virus Research of the Hepatitis B Foundation, Doylestown, Pennsylvania 18901,² Division of Gastroenterology, University of Michigan, 3912 Taubman Center, Ann Arbor, Michigan 48109-0362,³ Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, United Kingdom⁴

Received 23 July 2007/ Accepted 31 October 2007

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 [Gal-1-3Galβ1-(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.

Published ahead of print on 28 November 2007.