Immune response against protein epitopes modified with acetaldehyde and its clinical significance in alcoholoic liver diseases

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Acetaldehyde, the first metabolite of ethanol, is capable to bind various proteins followed by the formation of acetaldehyde adducts. This condensate is supposed to act as a neoantigen. We have recently demonstrated the appearance of acetaldehyde adducts in liver of experimental animals after chronic ethanol treatment, and we produced an experimental hepatitis in guinea pig by immunization with acetaldehyde adducts and treatment with free access to ethanol. However the structure of acetaldehyde adducts and its characteristics are still vague. To elucidate the binding site of anti-adducts antibody against the epitope on adducts, we established a cell line of hybridoma producing monoclonal antibody. This monoclonal antibody recognized condensate modified with high concentration of acetaldehyde (1-10 mM) but not those modified with low concentration of it (20-200 μM), whereas the polyclonal antibody produced by conventional method recognized both of them. Using the affinity-purified adducts by monoclonal or polyclonal antibody-liganded column, we examined the antibody titeres by ELISA. The elevation of antibody titer was more specific in chronic alcoholics, especially in patients with hepatic inflammatory change, when antibody was measured against the adducts purified by monoclonal antibody than against the adduct purified by polyclonal antibody. Namely, there exist different types of antibody according to the concentration of acetaldehyde to form the adducts. The concentration of acetaldehyde is thought to be much greater in the liver of alcoholics compared to the patient with non alcoholic liver disease. Actually we have immunohistochemically detected the adduct related to high concentration of acetaldehyde in the liver specimens of alcoholics. In conclusion, the appearance of adduct related to high concentration of acetaldehyde and the acquisition of immunity against it appear to be a characteristic feature in alcoholics with hepatic inflammation. Therefore, evaluation of circulating antibodies against protein epitope related to high concentration of acetaldehyde is helpful to know conditions of such types of liver disease seen in alcoholics.

Original languageEnglish
Pages (from-to)483-496
Number of pages14
JournalJapanese Journal of Alcohol Studies and Drug Dependence
Volume28
Issue number6
Publication statusPublished - 1993

Fingerprint

Acetaldehyde
alcoholism
Liver Diseases
Epitopes
Disease
Alcoholics
Antibodies
Proteins
Liver
Ethanol
Guinea
Monoclonal Antibodies
immunity
contagious disease
animal
Alcoholic Liver Diseases
Hybridomas
Hepatitis
evaluation
Anti-Idiotypic Antibodies

Keywords

  • Acetaldehyde adduct
  • Alcoholic liver diseases
  • Immune response

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Health(social science)

Cite this

@article{6ba7a8f5daa847f6a05938e291bec9c0,
title = "Immune response against protein epitopes modified with acetaldehyde and its clinical significance in alcoholoic liver diseases",
abstract = "Acetaldehyde, the first metabolite of ethanol, is capable to bind various proteins followed by the formation of acetaldehyde adducts. This condensate is supposed to act as a neoantigen. We have recently demonstrated the appearance of acetaldehyde adducts in liver of experimental animals after chronic ethanol treatment, and we produced an experimental hepatitis in guinea pig by immunization with acetaldehyde adducts and treatment with free access to ethanol. However the structure of acetaldehyde adducts and its characteristics are still vague. To elucidate the binding site of anti-adducts antibody against the epitope on adducts, we established a cell line of hybridoma producing monoclonal antibody. This monoclonal antibody recognized condensate modified with high concentration of acetaldehyde (1-10 mM) but not those modified with low concentration of it (20-200 μM), whereas the polyclonal antibody produced by conventional method recognized both of them. Using the affinity-purified adducts by monoclonal or polyclonal antibody-liganded column, we examined the antibody titeres by ELISA. The elevation of antibody titer was more specific in chronic alcoholics, especially in patients with hepatic inflammatory change, when antibody was measured against the adducts purified by monoclonal antibody than against the adduct purified by polyclonal antibody. Namely, there exist different types of antibody according to the concentration of acetaldehyde to form the adducts. The concentration of acetaldehyde is thought to be much greater in the liver of alcoholics compared to the patient with non alcoholic liver disease. Actually we have immunohistochemically detected the adduct related to high concentration of acetaldehyde in the liver specimens of alcoholics. In conclusion, the appearance of adduct related to high concentration of acetaldehyde and the acquisition of immunity against it appear to be a characteristic feature in alcoholics with hepatic inflammation. Therefore, evaluation of circulating antibodies against protein epitope related to high concentration of acetaldehyde is helpful to know conditions of such types of liver disease seen in alcoholics.",
keywords = "Acetaldehyde adduct, Alcoholic liver diseases, Immune response",
author = "Hirokazu Yokoyama",
year = "1993",
language = "English",
volume = "28",
pages = "483--496",
journal = "Arukoru kenkyu to yakubutsu izon = Japanese journal of alcohol studies & drug dependence",
issn = "1341-8963",
publisher = "Nihon Arukoru Igakkai/Japenese Medical Society of Alcohol Studies",
number = "6",

}

TY - JOUR

T1 - Immune response against protein epitopes modified with acetaldehyde and its clinical significance in alcoholoic liver diseases

AU - Yokoyama, Hirokazu

PY - 1993

Y1 - 1993

N2 - Acetaldehyde, the first metabolite of ethanol, is capable to bind various proteins followed by the formation of acetaldehyde adducts. This condensate is supposed to act as a neoantigen. We have recently demonstrated the appearance of acetaldehyde adducts in liver of experimental animals after chronic ethanol treatment, and we produced an experimental hepatitis in guinea pig by immunization with acetaldehyde adducts and treatment with free access to ethanol. However the structure of acetaldehyde adducts and its characteristics are still vague. To elucidate the binding site of anti-adducts antibody against the epitope on adducts, we established a cell line of hybridoma producing monoclonal antibody. This monoclonal antibody recognized condensate modified with high concentration of acetaldehyde (1-10 mM) but not those modified with low concentration of it (20-200 μM), whereas the polyclonal antibody produced by conventional method recognized both of them. Using the affinity-purified adducts by monoclonal or polyclonal antibody-liganded column, we examined the antibody titeres by ELISA. The elevation of antibody titer was more specific in chronic alcoholics, especially in patients with hepatic inflammatory change, when antibody was measured against the adducts purified by monoclonal antibody than against the adduct purified by polyclonal antibody. Namely, there exist different types of antibody according to the concentration of acetaldehyde to form the adducts. The concentration of acetaldehyde is thought to be much greater in the liver of alcoholics compared to the patient with non alcoholic liver disease. Actually we have immunohistochemically detected the adduct related to high concentration of acetaldehyde in the liver specimens of alcoholics. In conclusion, the appearance of adduct related to high concentration of acetaldehyde and the acquisition of immunity against it appear to be a characteristic feature in alcoholics with hepatic inflammation. Therefore, evaluation of circulating antibodies against protein epitope related to high concentration of acetaldehyde is helpful to know conditions of such types of liver disease seen in alcoholics.

AB - Acetaldehyde, the first metabolite of ethanol, is capable to bind various proteins followed by the formation of acetaldehyde adducts. This condensate is supposed to act as a neoantigen. We have recently demonstrated the appearance of acetaldehyde adducts in liver of experimental animals after chronic ethanol treatment, and we produced an experimental hepatitis in guinea pig by immunization with acetaldehyde adducts and treatment with free access to ethanol. However the structure of acetaldehyde adducts and its characteristics are still vague. To elucidate the binding site of anti-adducts antibody against the epitope on adducts, we established a cell line of hybridoma producing monoclonal antibody. This monoclonal antibody recognized condensate modified with high concentration of acetaldehyde (1-10 mM) but not those modified with low concentration of it (20-200 μM), whereas the polyclonal antibody produced by conventional method recognized both of them. Using the affinity-purified adducts by monoclonal or polyclonal antibody-liganded column, we examined the antibody titeres by ELISA. The elevation of antibody titer was more specific in chronic alcoholics, especially in patients with hepatic inflammatory change, when antibody was measured against the adducts purified by monoclonal antibody than against the adduct purified by polyclonal antibody. Namely, there exist different types of antibody according to the concentration of acetaldehyde to form the adducts. The concentration of acetaldehyde is thought to be much greater in the liver of alcoholics compared to the patient with non alcoholic liver disease. Actually we have immunohistochemically detected the adduct related to high concentration of acetaldehyde in the liver specimens of alcoholics. In conclusion, the appearance of adduct related to high concentration of acetaldehyde and the acquisition of immunity against it appear to be a characteristic feature in alcoholics with hepatic inflammation. Therefore, evaluation of circulating antibodies against protein epitope related to high concentration of acetaldehyde is helpful to know conditions of such types of liver disease seen in alcoholics.

KW - Acetaldehyde adduct

KW - Alcoholic liver diseases

KW - Immune response

UR - http://www.scopus.com/inward/record.url?scp=0027716557&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027716557&partnerID=8YFLogxK

M3 - Article

VL - 28

SP - 483

EP - 496

JO - Arukoru kenkyu to yakubutsu izon = Japanese journal of alcohol studies & drug dependence

JF - Arukoru kenkyu to yakubutsu izon = Japanese journal of alcohol studies & drug dependence

SN - 1341-8963

IS - 6

ER -