Studies on Non-Specifically Immunosuppressive Factors in Sera of Patients with Primary Hepatoma

Sera from patients with primary hepatoma markedly suppressed the normal lymphocyte response to phytohemagglutinin (PHA) as compared with normal sera. Fractionations of normal, hepatitis and hepatoma sera were carried out by DEAE cellulose column chromatography using a continuous concave gradient. The elution patterns of these sera were quite similar and separated into nine fractions. No differences between subfractions obtained from normal, hepatitis and hepatoma sera could be detected by a protein analysis employing immunoelectrophoresis and immunodiffusion. Inhibition of the PHA response of normal lymphocytes by the hepatoma sera, however existed in α-,β-globulin and albumin fractions. On the other hand, in the fractions from normal sera, α-, β-globulin fractions disclosed a similar degree of inhibition to the PHA response of normal lymphocytes, but the albumin fraction dismissed the inhibitory activity. Further investigations of these inhibitory fractions of hepatoma sera on Sephadex G-200 gel filtration showed that the α-globulin fraction with the highest degree of inhibitory activity contained carcinoembryonic protein (α-fetoprotein and ferritin) and Immunoregulatory α-globulin (IRA) protein. The albumin with a moderate degree of inhibitory activity contained α-2-macroglobulin. The carcinoembryonic proteins and α-2-macroglobulin. The carcinoembryonic proteins and α-2-macroglobulin obtained from patients with hepatoma exhibited a remarkable suppression of the PHA responses of mormal lymphocytes. The electro-focusing pattern of α-2-macroglobulin fractions obtained from normal, hepatitis and hepatoma sera showed definite differences in protein composition. It is suggested that the function of lymphocytes in patients with primary hepatoma is be regulated by a variety of humoral factors