HLA-B8, immunoglobulins, and antibody responses in alcohol-related liver disease.

Abstract

SUMMARY Ninety-two British, caucasian, alcoholic patients with liver disease were grouped on the basis of hepatic histology into fatty change, hepatitis with or without cirrhosis, and cirrhosis alone. Men with alcoholic hepatitis with or without cirrhosis showed an increased incidence of the histocompatibility antigen HLA-B8 (P < 0-02). Increased measles antibody titres were found in patients with cirrhosis with or without hepatitis and were associated with the B8 phenotype in both sexes. Rubella antibody titres and percentage DNA-binding were raised in patients with cirrhosis and showed no association with the B8 phenotype. Concentrations of 1gM and IgA were raised in patients with steatosis and with hepatitis, while in patients with cirrhosis IgG concentrations were also increased. Low titres of autoantibodies were found in all histological groups.It is possible that the development of hepatitis in response to alcohol abuse may be influenced, at least in men, by a gene linked to the B locus. Otherwise, immune processes associated with alcoholrelated liver disease are probably secondary phenomena.The liver damage seen in alcoholic subjects results from the direct hepatotoxic effect of ethanol.' The development of alcoholic cirrhosis is often preceded by alcoholic hepatitis,2 although alcoholic cirrhosis may develop without the hepatitic stage.3Only 20% of alcoholic subjects develop liver disease; therefore, constitutional or genetic factors may be concerned in this individual susceptibility to develop cirrhosis and may also influence the 'route' by which it develops.The role of genetically determined immunological factors in the pathogenesis of alcohol-related liver disease has recently received much attention. Conflict has arisen, in particular, regarding the prevalence and importance of the histocompatibility antigen HLA-B8.4-8We have therefore screened a group of 92 alcoholics with liver disease of varying severity for B8 in an attempt to clarify this situation. In addition, we have measured antibodies to rubella, measles, smooth muscle, nuclear and mitochondrial antigens, and serum immunoglobins for further evidence of an altered immune status in these patients. Particular attention has been paid to the relationship between these various indices and the histological changes on liver biopsy.Received for publication 13 November 1979 Patients and methods Ninety-two British, caucasian, alcoholic patients (68 men: 24 women) who had taken more than 100 g ethanol per day for at least five years were grouped, on the basis of liver histology, into fatty change only, alcoholic hepatitis with or without cirrhosis, or cirrhosis alone. All patients were abusing alcohol up to the time of hospitalisation, and liver biopsies were taken within one week of admission. Suitable investigations were undertaken to exclude other causes of liver disease.

Prevalence and significance of autoantibodies in patients with alcoholic liver disease

“…Autoantibodies were detected in ALD patients decades ago. The observed frequency in previous studies varied but overall it seemed to occur in 25–40% of the patients, which was significantly lower than that of ours (63.8%). This probably reflects the fact that with the in‐depth study of non‐viral chronic liver diseases, more clinicians have realized the immune mechanisms involved in the ALD and therefore more patients have undertaken this test.…”

Increased spontaneous and lymphokine-conditioned IgA and IgG synthesis by B cells from alcoholic cirrhotic patients

“…Clear evidence demonstrates that the liver alteration is induced by the toxic effects of ethanol (1). However, several abnormalities in the immune systems of alcoholic cirrhosis (AC) patients have been described (2)(3)(4)(5)(6)(7)(8)(9). The cellular and molecular bases of these immune alterations, as well as their pathogenic significance and clinical implications, remain unknown.…”

Increased Serum Concentration of IgA2 Subclass and IgA2/IgA1 Ratio: Specific Markers of Chronic Alcoholic Abuse?

“…This their pathogenic significance and clinical implications abnormality may be related to overproduction of IgA remain unknown. Hypergammaglobulinaemia, mainly and i™™ 6 disturbances in patients with alcoholic enhancement of the serum IgA concentration, is a comr dlsease · mon immunological finding in patients with alcoholic We have studied serum IgA, IgAl, IgA2 and IL-6 conliver cirrhosis (5)(6)(7). It has been demonstrated that this centrations in heavy alcohol drinkers without clinical high immunoglobulin concentration is not due to abnor-liver disease in comparison with alcoholic liver cirrhosis mal catabolism of IgA (1)(2).…”

“…Abnormalities in the immune systems of alcoholic liver in P atients with alcoholic liver cirrhosis < 10 )· IL ' 6 Ρ ΓΟ ' cirrhosis patients have been described (1 -4). However, duction Correlates closely with IgA serum levels.…”