Increased levels of galactose-deficient anti-Gal immunoglobulin G in the sera of hepatitis C virus-infected individuals with fibrosis and cirrhosis

Anand S. Mehta, Ronald E. Long, Mary Ann Comunale, Mengjun Wang, Lucy Rodemich, Jonathan Krakover, Ramila Philip, Jorge A. Marrero, Raymond A. Dwek, Timothy M. Block

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

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 [Galα-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.

Original languageEnglish (US)
Pages (from-to)1259-1270
Number of pages12
JournalJournal of virology
Volume82
Issue number3
DOIs
StatePublished - Feb 2008

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Mehta, A. S., Long, R. E., Comunale, M. A., Wang, M., Rodemich, L., Krakover, J., Philip, R., Marrero, J. A., Dwek, R. A., & Block, T. M. (2008). Increased levels of galactose-deficient anti-Gal immunoglobulin G in the sera of hepatitis C virus-infected individuals with fibrosis and cirrhosis. Journal of virology, 82(3), 1259-1270. https://doi.org/10.1128/JVI.01600-07