Antibodies against acetaldehyde-modified protein epitopes in human alcoholics

Authors

  • Onni Niemelä,

    1. Departments of Pharmacology and Medicine, University of Toronto, Toronto General Hospital and Addiction Research Foundation of Ontario, Toronto, Ontario, Canada M5S 2S1
    Current affiliation:
    1. Department of Medical Biochemistry, University of Oulu, Kajaanintic 52A, 90220 Oulu, Finland
    Search for more papers by this author
  • Felix Klajner,

    1. Departments of Pharmacology and Medicine, University of Toronto, Toronto General Hospital and Addiction Research Foundation of Ontario, Toronto, Ontario, Canada M5S 2S1
    Search for more papers by this author
  • Hector Orrego,

    1. Departments of Pharmacology and Medicine, University of Toronto, Toronto General Hospital and Addiction Research Foundation of Ontario, Toronto, Ontario, Canada M5S 2S1
    Search for more papers by this author
  • Eva Vidins,

    1. Departments of Pharmacology and Medicine, University of Toronto, Toronto General Hospital and Addiction Research Foundation of Ontario, Toronto, Ontario, Canada M5S 2S1
    Search for more papers by this author
  • Laurence Blendis,

    1. Departments of Pharmacology and Medicine, University of Toronto, Toronto General Hospital and Addiction Research Foundation of Ontario, Toronto, Ontario, Canada M5S 2S1
    Search for more papers by this author
  • Yedy Israel Ph.D.

    Corresponding author
    1. Departments of Pharmacology and Medicine, University of Toronto, Toronto General Hospital and Addiction Research Foundation of Ontario, Toronto, Ontario, Canada M5S 2S1
    • Department of Pharmacology, Medical Sciences Building, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Search for more papers by this author

Abstract

Acetaldehyde, the primary metabolite of ethanol, binds covalently to proteins forming condensation products which have been recently shown to be immunogenic. To assess whether an antibody response against acetaldehyde-modified protein epitopes is associated with alcoholic liver disease, the serum immunoreactivity against proteins modified in vitro by acetaldehyde and against the corresponding unmodified proteins was measured by an enzyme-linked immunosorbent assay in 58 alcoholics with varying degrees of liver damage. Alcoholics showed significantly higher titers against protein-acetaldehyde conjugates than against the unmodified protein, independent of the nature of the carrier protein. The highest titers occurred in alcoholic hepatitis patients. Sera of patients with chronic hepatitis of nonalcoholic origin and of healthy controls also reacted with acetaldehyde conjugates, but their titers were significantly lower than those in alcoholic hepatitis patients. Our data support the idea that binding of acetaldehyde to proteins in humans generates antigenic determinants which trigger a corresponding immune response against such epitopes and suggest that this humoral immune response may be implicated in autoantibody formation and liver damage associated with excessive alcohol consumption.

Ancillary