Niemelä O, Klajner F, Orrego H, Vidins E, Blendis L, Israel Y
Department of Pharmacology, University of Toronto, Toronto General Hospital, Ontario, Canada.
Hepatology. 1987 Nov-Dec;7(6):1210-4. doi: 10.1002/hep.1840070607.
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.
乙醛是乙醇的主要代谢产物，它与蛋白质共价结合形成缩合产物，最近研究表明这些产物具有免疫原性。为了评估针对乙醛修饰的蛋白质表位的抗体反应是否与酒精性肝病相关，我们采用酶联免疫吸附测定法，检测了58例不同程度肝损伤的酗酒者血清中针对体外经乙醛修饰的蛋白质及相应未修饰蛋白质的免疫反应性。酗酒者针对蛋白质 - 乙醛缀合物的滴度显著高于针对未修饰蛋白质的滴度，且与载体蛋白的性质无关。最高滴度出现在酒精性肝炎患者中。非酒精性来源的慢性肝炎患者和健康对照者的血清也与乙醛缀合物发生反应，但其滴度显著低于酒精性肝炎患者。我们的数据支持这样一种观点，即乙醛在人体内与蛋白质结合会产生抗原决定簇，从而引发针对此类表位的相应免疫反应，并表明这种体液免疫反应可能与自身抗体形成以及过量饮酒相关的肝损伤有关。
