concanavalin-a and Hepatitis--Viral--Human

Acute non-A, non-B hepatitis developed in twelve patients with primary hypogammaglobulinaemia during treatment with intravenous gammaglobulin prepared by Cohn fractionation of pooled plasma. The illness was clinically and histologically identical to the short-incubation non-A, non-B, hepatitis observed in haemophilic patients receiving factor VIII concentrates. Most of the patients were symptomless, but 10 months after onset ten of the twelve still had abnormal liver function. The occurrence of non-A, non-B hepatitis in agammaglobulinaemics indicates that humoral mechanisms are not essential for production of hepatocyte necrosis in this infection. This outbreak emphasises the need for a screening test to identify the agent in blood products, and shows that Cohn fractionation of plasma does not always inactivate the agent. Furthermore, the finding that the virus can be transmitted in IgG concentrates suggests either that the general population has a very low level of antibodies to the putative virus or that such antibodies are not virus-neutralising.

Topics: Agammaglobulinemia; Aspartate Aminotransferases; Clinical Trials as Topic; Concanavalin A; Female; Hepatitis C; Hepatitis, Viral, Human; Humans; Immunoglobulins; Injections, Intramuscular; Injections, Intravenous; Phenotype; T-Lymphocytes

1. Using crossed immunoaffinity electrophoresis with free concanavalin A in the first dimension, we studied the microheterogeneity of alpha 1-antichymotrypsin due to various glycoforms in sera from patients with various liver diseases and after liver transplantation. 2. Studies by isoelectric focusing and immunoblotting and by crossed immunoelectrophoresis without concanavalin A in the first dimension allowed us to show that there is no dramatic variation in electrophoretic heterogeneity of alpha 1-antichymotrypsin in the serum of patients with liver diseases or after liver transplantation when compared with that of normal subjects. Therefore the heterogeneity observed in crossed immunoaffinity electrophoresis is due to various interactions with concanavalin A. 3. The results were expressed as the ratio of concanavalin A non-reactive glycoforms plus concanavalin A weakly reactive glycoforms to concanavalin A reactive glycoforms, called R alpha 1-ACT. R alpha 1-ACT was significantly higher in patients with cirrhosis (n = 53) when compared with normal subjects (n = 30). The median R alpha 1-ACT was 1 (range 0.72-1.25) in normal subjects. It was 1.6 (range 1.18-3.02), 1.45 (range 0.65-4.12) and 2.24 (range 1.03-19) in cirrhosis of Child's grade A, B and C, respectively. There was a dramatic decrease in glycoforms with mostly biantennary glycans in some patients with Child's grade C cirrhosis. Serum levels of alpha 1-antichymotrypsin were lower than normal only in some patients with Child's grade C cirrhosis. 4. Among the patients with acute viral hepatitis studied (n = 17), five were studied longitudinally.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Aged, 80 and over; alpha 1-Antichymotrypsin; Concanavalin A; Female; Glycosylation; Hepatitis, Viral, Human; Humans; Immunoelectrophoresis, Two-Dimensional; Isoelectric Focusing; Liver Cirrhosis; Liver Diseases; Liver Transplantation; Male; Middle Aged

We investigated lymphocyte suppressor cell activity in 53 patients with acute and chronic liver diseases. Suppressor cells were generated by preincubation of peripheral blood mononuclear cells (PBM) with concanavalin A (Con A) for 48 hr. Suppressor cell activity was evaluated by inhibition of Con A-stimulated blast transformation and by inhibition of pokeweed mitogen-induced immunoglobulin (Ig) synthesis of fresh allogeneic normal PBM in the second-set cultures. Of 29 patients with chronic active liver diseases (CALD), defective suppressor cell activities were observed in eight cases (28%) for Ig synthesis and 16 cases (55%) for blast transformation study. The suppressor cell activities were decreased in two (22%) of nine cases with chronic persistent hepatitis and one (17%) of six cases with inactive cirrhosis for both Ig synthesis and blast transformation. In contrast, suppressor activities were inducible in all nine patients with acute viral hepatitis. The histocompatibility antigen DR4 was significantly increased in CALD patients, but there was no correlation between this antigen and suppressor cell activity. These findings suggest that altered lymphocyte suppressor cells in patients with CALD may contribute to the continuing liver cell injury in this disease.

Topics: Acute Disease; Adult; Chronic Disease; Concanavalin A; Hepatitis, Viral, Human; HLA Antigens; Humans; Immunoglobulins; Liver Diseases; Lymphocyte Activation; Middle Aged; Pokeweed Mitogens; T-Lymphocytes, Regulatory

The response of peripheral blood T lymphocytes to concanavalin A (Con A) assessed by the production of leukocyte migration inhibitory factor (LMIF), was studied in patients with acute viral hepatitis type B and in patients with chronic aggressive hepatitis carrying hepatitis B surface antigen (HBsAg). Lymphocytes from patients in the acute period of the disease and in severely active chronic aggressive hepatitis showed the ability to respond by LMIF production while lymphocytes from patients with moderately active chronic aggressive hepatitis were unable to do so. In parallel, it was shown that lymphocytes from the latter group of patients were capable of suppressing Con-A induced LMIF production. Thus, mitogen-induced mediator production may be a useful parameter in the further characterization of chronic viral hepatitis.

Topics: Adult; Concanavalin A; Hepatitis, Viral, Human; Humans; Immunity, Cellular; Leukocyte Migration-Inhibitory Factors; Lymphokines; Middle Aged; T-Lymphocytes

Suppressor cell function was studied in twenty-nine patients with chronic active hepatitis (CAH) in relation to possible aetiological causes and activity of liver disease. All fifteen patients with evidence of viral aetiology (ten HBsAg-positive CAH and five non-A, non-B CAH) showed normal suppressor cell function independently of severity of liver damage. In contrast, fourteen patients with HBsAg-negative CAH, including four cases with circulating antibodies to the hepatitis B virus, demonstrated a significant reduction in supprpessor cell activity compared to control subjects. No significant difference was found in this group between cases with and without circulating autoantibodies. In four out of five HBsAg-negative patients tested serially suppressor cell defect correlated with disease activity suggesting an abnormality in the regulation rather than a depletion of suppressor cells. These results suggest that different mechanisms are responsible for autoimmunity to the liver in virus and non-virus-related CAH.

Topics: Adolescent; Adult; Concanavalin A; Dose-Response Relationship, Drug; Female; Hepatitis; Hepatitis B; Hepatitis, Viral, Human; Humans; Lymphocyte Activation; Male; Middle Aged; T-Lymphocytes, Regulatory

Depressed phytohaemagglutinin and concanavalin-A responsiveness was found in patients with acute viral hepatitis (VH) when a suboptimal mitogen stimulus was used. Normal responsiveness was observed with optimal mitogen stimulation. These findings were independent of extrinsic serum inhibitors. When viral hepatitis lymphocytes were preincubated before mitogen addition an enhanced responsiveness similar to the control group occurred. These in vitro findings are in favour of a primary defect in lymphoproliferation in viral hepatitis and do not suggest the presence of reversible suppressive influences such as an excess of short-lived suppressor cells or the presence of cell bound inhibitors. In chronic active hepatitis (CAH) lymphoproliferation induced by immediate mitogen stimulation was similar to control studies. However when CAH cells were preincubated before mitogen addition, enhanced responsiveness significantly greater than in controls occurred. It is suggested that suppressive influences are present in CAH and that their effect can be reversed by cellular preincubation.

Topics: Adolescent; Adult; Aged; Cells, Cultured; Child; Child, Preschool; Concanavalin A; Female; Hepatitis; Hepatitis, Viral, Human; Humans; Lymphocyte Activation; Male; Middle Aged; Phytohemagglutinins; Pokeweed Mitogens