Autoantibodies in Alcohol-Related Tissue Diseases

This chapter describes autoantibodies in alcohol-induced tissue diseases. As the immune system has a key role in regulating inflammation associated with chronic liver diseases, there is a growing interest in understanding the mechanisms by which alcohol abuse might promote immune reactions toward the liver. Early studies suggested that the interaction of acetaldehyde with hepatic proteins stimulates antibody production in patients with Alcoholic Liver Disease (ALD). Further investigations suggest that the binding of hydroxyethyl free radicals (HER) to cytochrome P4502E1 (CYP2E1) induces the production of specific antibodies in either alcohol-fed rats or alcoholic patients. Moreover, ALD patients have increased titers of antibodies directed against protein adducts with different lipid peroxidation products and against antigens derived from the combination of malonildialdehyde and acetaldehyde. Oxidative stress also has a role in promoting the autoimmune reactions often associated with ALD, because anti-phospholipid antibodies present in large fraction of ALD patients are recognized as antigens oxidized phospholipids. Furthermore, CYP2E1 modification by HER promotes the development of anti-CYP2E1 autoantibodies. This effect is greatly enhanced by an impaired control of T lymphocyte proliferation because of the genetic polymorphisms of the immunoregulatory molecule CTLA-4.