Studies on Hypergammaglobulinemia in Liver Diseases

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To clarify the significance of hypergammaglobulinemia in liver diseases, the levels of immunoglobulins in the sera of patients with various liver diseases were determined and some experiments were carried out as follows. 1) Of a total of 108 patients, 33 had acute hepatitis, 43 chronic hepatitis and 32 liver cirrhosis. γ-G and γ-M in their sera were determined by the anti-globulin inhibition test and γ-A by the double diffusion method in agar plate.(TABLE I) i) In acute hepatitis, r-G slightly increased in around 2 weeks after the onset, r-M moderately 1 week or 6 later and γ-A moderately in around 6 weeks. Then all returned to normal 2 to 3 months later when favorably progressed.(Fig. 1) ii) Agglutinin test of virus-latex particles (virus isolated from the sera of volunteers who had been inoculated with icterogenic plasma pool was adsorbed onto latex particles) was positive in acute hepatitis, chronic hepatitis and liver cirrhosis, but also in renal diseases. However, no relationship was found between agglutinin titers and levels of immunoglobulins in the course of acute hepatitis. iii) In chronic hepatitis, γ-G and γ-A were moderately elevated and γ-M was markedly high. In liver cirrhosis, γ-G markedly increased, and γ-A and γ-M were moderately high.(Fig. 2) iv) γ-M levels were correlated with titers of rheumatoid factor in liver cirrhosis and chronic hepatitis, while high levels of γ-M in acute hepatitis was not accompanied by rheumatoid factor. It was therefore suggested that increased γ-M in both groups, i. d. acute hepatitis and cirrhosis, is different from each other in quality. v) In 5 patients with chronic hepatitis and 3 with liver cirrhosis, azathiopurine was given orally in the dose of 100mg per day for 2 to 4 weeks. Then immunoglobulin levels were suppressed in most cases. 2) To observe the ability to produce antibody by a cirrhotic rat, 8 carbon tetrachlorideinduced cirrhotic rats were examined with 13 normal rats as the control. One ml of suspension of freshly washed sheep erythrocytes (0.25%) was intravenously given, and the amount of sheepcell hemolysin were determined by serial two-fold dilution method by using an appropriate unit of complement in each tube. Titers in the sera of cirrhotic rats were markedly increased, showing 4,200 dilutions on the average, and 772 dilutions in the controls.(Fig. 3) 3) Patients with chronic liver diseases were also examined with a view to production of antibodies by using 9 cases with chronic hepatitis, 9 with liver chrrhosis, 2 of Banti's syndrome and 14 normal subjects. 0.5ml of standard alum-precipitated tetanus toxoid was subcutaneously given twice at intervals of 6 weeks. Two weeks after the last injection, the amount of tetanus antitoxin was detemined by the neutralizing method using mice. The mean value in patients with chronic liver diseases was 0.188 I. U./ml and 0.055 I. U. in the normal.(Fig. 4) 4) The incorporation rates of 14C-leucine in vitro into γ-G in liver slices of the rat (cirrhotic one induced by feeding Penicillium islandicum Sopp inoculated rice and the normal) were determined, when these were incubated with Krebs-Ringer phosphate buffer (pH 7.4) for 2 hr. γ-G was obtained by the immunological method from the supernatant fraction of the liver tissue. The incorporation rate was significantly increased in the cirrhotic liver tissue, as compared with that in the normal liver tissue.(TABLE II) 5) From these results, it seems that immunoglobulin levels in the course of acute hepatitis are similiar to those in common acute infectious diseases, while hypergammaglobulinemia in chronic hepatitis and liver cirrhosis is due to unusual immunological capacity: hyperimmunity.
Japan Society of Clinical Chemistryの論文

Studies on Hypergammaglobulinemia in Liver Diseases

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