HLA antigens as immunogenetic markers of alcoholism in Japan

We think that physicians are usually only alerted to the sensitivity of tests and should be better trained to use the predictive value because Bayes’ theorem takes into account the non-specificity (but also the incidence of the sickness so that the results cannot always be directly extrapolated from one population to another).

29

HLA ANTIGENS IN JAPAN

AS IMMUNOGENETIC

MARKERS

OF ALCOHOLISM

YOHSUKE SHIGETA*, HIROMASA ISHII”, SATOSHl TAKAGI, YOSHITAKE, TAKEMICHI HIRANOa, HIROAKI KOHNO and TSUCHIYAa National Institute on Alcoholism, Yokosuka-City, Medicinea, Keio University, Tokyo (Japan)

Kanagawa-Pref.,

YASUTOSHI MASAHARU

and School

of

Chronic alcoholism is thought to originate from many complicated factors such as social, psychological and biological ones. Not all those who drink rather heavily necessarily become alcoholics, and it is also known that there is an individual susceptibility to liver cirrhosis, a major complication in alcoholics. Recently, an immunological mechanism has been implicated in the pathogenesis of alcoholic cirrhosis. Therefore the present study was designed to clarify the pattern of HLA antigens, major histocompatibility complex, among chronic alcoholics especially in relation to hepatic lesions. The subjects consisted of 94 chronic alcoholics admitted to the division of internal medicine or psychiatry, National Kurihama Hospital (National Institute on Alcoholism, Japan). They were all admitted to the hospital for detoxication and rehabilitation. The mean daily alcohol intake was approximately 150 g of 20 years’ duration. Blood HBs antigens were all negative. As for controls, blood was supplied from 80 normal healthy subjects. HLA typing was done by the standard microcytotoxicity assay according to NIH. Japanese originated HLA antisera from Bohsei Sangyo Co. Ltd. and Hoechst Co. Ltd. were used. The phenotype frequency (PF) of the controls was similar to the results reported at the 7th International Workshop of HLA. Concerning the A and B loci, there was no significant change of PF in the HLA antigen typing between controls and chronic alcoholics. However, HLA C loci were detected mainly with Cw3 and Cw4 and there was a significant difference in the PF of Cw3 between chronic alcoholics and controls (58.5% in alcoholics us. 30.0% in controls), and the corrected p value was less than 0.05 with relative risk value being 3.29. Furthermore, all alcoholics were subdivided according to hepatic morphology and the PF of HLA antigens was examined. In the cirrhotic group there were some increasing tendencies of A2, A26 and All, and decreasing tendency of Aw24. But these changes were not statistically significant. On the contrary, a significantly high frequency of HLA

34

Cw3 was found in patients with hepatitis (64%) compared to controls (30%). There was also an increase of Cw3 PF in the liver cirrhosis group (59% in cirrhosis group us. 30% in controls). In conclusion, chronic alcoholics have a significantly high phenotype frequency of HLA Cw3. This characteristic feature becomes even more distinct in alcoholics with severe hepatic lesions. Supported

by grants from the Ministry

of Health and Welfare.

30 MITOCHONDRIAL GLUTAMIC-OXALOACETIC TRANSAMINASE AND MICROSOMAL GAMMA-GLUTAMYLTRANSPEPTIDASE: ENHANCED SERUM ACTIVITY AND SIGNIFICANCE AS MARKERS OF ALCOHOLISM HIROMASA MASAHARU Department

ISHII*, FUMIO TSUCHIYA

OKUNO,

of Internal Medicine,

YOKO EBIHARA,

Keio University,

Tokyo

TOSHIKAZU

TAKAGI

and

160 (Japan)

Among a number of enzymes only a few are used for the diagnosis of liver diseases. In alcoholic liver disease, it is well-known that serum glutamicoxaloacetic transaminase (GOT) activity is increased and its activity is preferentially higher than glutamic-pyruvic transaminase (GPT) activity. Moreover gamma-glutamyltranspeptidase (GGTP) has recently been used as a sensitive index for heavy drinking. However, the mechanism of these increases still remains to be elucidated. Since the subcellular localization of these two enzymes varies (that is, GOT is present in both mitochondrial and cytosolic fractions and GGTP is chiefly in the microsomal fraction), it is conceivable that the mechanism of the enhanced activity is different for each enzyme. In this study we investigated some of the effects of ethanol on the activity of GOT and GGTP in sera of alcoholics. First we observed the liver function test in alcoholics and found that serum GOT activity was elevated in 60% of alcoholics, whereas serum GPT activity was increased in 30%. However, an abnormal level of GGTP was found in more than 90% of the cases. In order to clarify the mechanism of a preferential increase in serum GOT activity and to assess the contribution of mitochondria-derived GOT (mGOT) to this increase, mGOT was measured by column chromatography. In controls, mean mGOT activity was 3.7 U, whereas there was a significant increase in mGOT activity in various liver diseases (9.8 U in alcoholics, 24.9 U in acute hepatitis, 12.7 U in liver cirrhosis and 9.8 U in chronic hepatitis). Furthermore, mGOT activity was expressed as a percentage of total GOT activity. The mGOT/GOT ratio was largest in alcoholics (19.1%) followed by liver cirrhosis (14.3%), chronic hepatitis (11.5%) and acute hepatitis (5.9%). Elevated mGOT activity did not correlate well with the activity of creatine phosphokinase. We have further done animal experiments using female rats