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To evaluate the interactions between circulating immune complexes (CIC) and lymphoid cells in primary biliary cirrhosis (PBC), we determined (1) whether antibodies to lymphocytes in PBC serum, independent of CIC, could account for binding in the Raji cell assay for CIC and (2) whether CIC or other humoral factors in PBC serum could interact with lymphoid cells to alter their function. We found that three quarters of CIC positive PBC sera bound specifically to Raji cells via complement receptors, while only one quarter had antibodies to lymphoid cells or Raji cells devoid of complement receptors. We also demonstrated factors which inhibited cell-mediated cytotoxicity and suppressor cell activity in PBC sera; however, we found no correlation between the level and presence of CIC or of lymphocyte antibodies and the level or presence of these serum inhibitory factors. Thus, although the detection of CIC in PBC is not artifactual, the contribution of CIC and other serum factors to the other immunological aberrations in PBC remains to be elucidated. [ABSTRACT FROM AUTHOR]

To determine whether abnormalities of immunoregulatory T cells are associated with primary biliary cirrhosis, we characterized peripheral blood mononuclear cells in 16 patients with primary biliary cirrhosis and compared them with 30 normal controls. For this analysis we used monoclonal antibodies to the surface antigens on helper/inducer (T4+) and suppressor (T8+) T cell subsets and to a common T cell antigen (T3+). In contrast to normal persons, patients with primary biliary cirrhosis had reduced percentages of T3+ cells. More importantly, there was a relative decrease in helper/inducer (T4+) cells in 9/16 patients and a decrease in suppressor (T8+) cells in 5/16 patients. Furthermore, clinical studies indicated that patients with a decreased suppressor cell population (increased T4+:T8+ ratio) had more advanced disease, as reflected by serum bilirubin levels [P<0.05) and histological changes in the liver (P<0.001), than those patients with a reduced helper T cell population (decreased T4+:T8+ ratio). These data suggest that abnormalities of immune responsiveness in primary biliary cirrhosis may have a more complex origin than a uniform alteration in one immunoregulatory T-cell subset and that these immunoregulatory cell changes vary according to the severity of the disease. [ABSTRACT FROM AUTHOR]

Elevated serum immunoglobulin levels are a frequent finding in patients with severe alcoholic liver disease. We measured in vitro peripheral blood lymphocyte IgG synthesis by radioimmunoassay in 13 patients with severe alcoholic liver disease and hypergammaglobulinaemia and in normal control subjects. We found an increase in spontaneous IgG synthesis compared to controls (P>0.001). On the other hand, there was no difference between groups in percentage stimulation of IgG production by B cells exposed to pokeweed mitogen. We also searched for defects in concanavalin A (Con A) induced suppressor T cell activity. There was no difference between patients with alcoholic liver disease and controls in the capability of such suppressor T cells to inhibit the response of allogeneic cells to a T cell mitogen. Similarly, we examined the capability of Con A-induced suppressor T cells to inhibit pokeweed mitogen-stimulated IgG synthesis by both autologous and allogeneic responder cells and observed no difference between alcoholic patients and controls. Thus these measured suppressor T-T and T-B cell interactions appeared no different from those in control subjects. Our studies suggest, therefore, that B cell IgG synthesis in vitro is enhanced in alcoholic liver disease. Furthermore, the capability to induce suppressor T cells which affects both T and B cell function appears intact; a finding in contrast to our previous observation in chronic active hepatitis. The above investigations suggest that enhanced spontaneous IgG synthesis in vitro may result from intense antigenic stimulation in vivo. [ABSTRACT FROM AUTHOR]

Resulting directly from the discovery of virus-related antigens, rapid progress has marked the last decade of viral hepatitis research. The hepatitis B virion has been tentatively identified as a DNA virus with an endogenous DNA polymerase, and new serological markers for type B hepatitis have been discovered. Hepatitis A antigen has been identified on a virus-like particle thought to be the hepatitis A virion. Progressively more sophisticated assays for hepatitis antigens and antibodies have been applied to the study of viral hepatitis epidemiology and biochemical-biophysical characterization of the agents. Most recently, knowledge learned from such studies has been exploited to develop a prototype non-infectious but immunogenic hepatitis B vaccine using hepatitis B surface antigen (HBsAg) purified in large quantities from chronic HBsAg carriers. Especially exciting is the prospect, suggested by serological studies of viral hepatitis, that hepatitis viruses besides hepatitis A and B viruses will be identified. [ABSTRACT FROM PUBLISHER]

Twenty-eight health care workers who had a poor antibody response when initially vaccinated with hepatitis B vaccine were revaccinated with three additional 20-microgram doses. Eight of the twenty nonresponders, who had levels of antibody to hepatitis B surface antigen (anti-HBs) of less than 8 estimated radioimmunoassay (RIA) units, and all 8 of the hyporesponders, who had anti-HBs levels of 8 or 16 RIA units, attained anti-HBs levels of 36 RIA units or more after revaccination. Tests for HLA-A, B, C, and DR; for complement proteins C2, C4A, C4B, and BF; and for the erythrocyte enzyme glyoxalase I were done in 17 nonresponders and 3 hyporesponders. Nine (45%) had HLA-DR7 and 8 (40%) had HLA-DR3, compared with an expected rate of 23% in the general population. At least one of two extended haplotypes (B44, DR7, FC31 or B8, DR3, SCO1) were detected in 6 of the 9 who did not respond to revaccination, compared with 2 of 11 who responded to a second course of vaccine. Poor responders to vaccine may benefit from revaccination, and genetic factors may modulate the immune response to vaccination. [ABSTRACT FROM AUTHOR]

In a double-blind trial, we randomly assigned 1330 high-risk health care personnel to receive three 20-micrograms doses of hepatitis B vaccine or placebo. Among vaccine recipients 58% responded within 1 month and 97% within 9 months; there was no difference in immune response to the vaccine between men and women. Efficacy was evaluated after a mean follow-up of only 13.2 months, just before the vaccine was released commercially. Five hepatitis B infections were identified in placebo recipients and one in a vaccine recipient. Although the number of infections was too small to allow confident conclusions about protective efficacy of the vaccine, we saw a 67% reduction in the need for hepatitis B immune globulin after accidental hepatitis B inoculation in the vaccine group (relative risk, 5.08; 95% confidence intervals, 1.3 to 19.9). Minor side effects occurred with equal frequency after vaccine (28.7%) and placebo (27.2%) injections; no participant had a severe adverse reaction. Vaccination with the 20-micrograms hepatitis B vaccine was highly immunogenic and safe in health care workers. [ABSTRACT FROM AUTHOR]

Prompted by reports associating essential mixed cryoglobulinemia with hepatitis B, we tested for hepatitis B markers in serum and cryoprecipitates and searched for virus particles by electron microscopy in cryoprecipitates from 12 patients with essential mixed cryoglobulinemia and 22 control subjects with mixed cryoglobulinemia secondary to recognized disease processes. None of the patients with essential cryoglobulinemia had detectable serum hepatitis B surface antigen (HBsAg) or antibody (anti-HBs), whereas five of the 22 patients with secondary cryoglobulinemia were positive for either HBsAg or anti-HBs. In cryoprecipitates from 10 patients with essential cryoglobulinemia, we could not detect HBsAg by radioimmunoassay or virus particles by electron microscopy, but one cryoprecipitate was anti-HBs-positive; however, four of 12 cryoprecipitates from patients with secondary cryoglobulinemia were positive for HBsAg or anti-HBs. Evidence of liver disease was present in similarly small proportions of both groups. Thus, in almost all our patients, essential mixed cryoglobulinemia was unrelated to hepatitis B infection. [ABSTRACT FROM AUTHOR]

To determine whether skin deposition of circulating immune complexes contributes to prodromal urticaria of acute hepatitis B, we studied two patients with hepatitis B who presented with urticaria and fever. During the urticarial prodrome but not thereafter, we found activation of both classic and alternative complement pathways. Hepatitis B surface antigen (HBsAg)-antibody complexes were identified (by electron microscopy) in cryoprecipitates from both patients and IgG (by immunodiffusion) in cryoprecipitates of one patient during urticaria. Light and electron microscopy of involved urticarial skin revealed necrotizing venulitis in both patients. Immunofluorescence microscopy showed fibrin within involved cutaneous vessel walls in one patient and C3, IgM, and HBsAg, which were not detected in simultaneously obtained uninvolved skin, in both patients. Our findings suggest that deposition of circulating immune complexes containing HBsAg is important in the pathogenesis of urticaria associated with acute hepatitis B virus infection. [ABSTRACT FROM AUTHOR]

Four hundred sixty patients and staff from 15 U.S. dialysis centers were surveyed by the immune adherence hemagglutination technique for antibody to hepatitis A antigen (anti-HA). The age-standardized anti-HA prevalence was 42.9% in patients and 42.1% in staff. These rates are almost identical to those of socioeconomically comparable urban volunteer blood donors never exposed to dialysis settings. There was no correlation between anti-HA prevalences and duration of dialysis treatment or employment. Among 100 patients and staff followed for 1 year 92% to 94% did not change their anti-HA status. The prevalence of anti-HA was identical in subjects with past histories of multiple blood transfusions or accidental inoculations with blood-contaminated instruments and in those without such histories. We conclude that hepatitis A virus rarely if every spreads by parenteral mechanisms, that there is no epidemiologic evidence confirming the existence of chronic hepatitis A viremic carrier states, and that hemodialysis does not play a significant role in the spread of type A hepatitis. [ABSTRACT FROM AUTHOR]

We studied serologically 45 adults who had sporadic acute viral hepatitis that was hepatitis B surface antigen (HBsAg) negative. Two cases were due to hepatitis B virus, as demonstrated by the appearance of antibody to hepatitis B core antigen. In three other patients, the serologic pattern was inconclusive. Of 40 non-B cases, 20 were type A hepatitis and 20 were non-A, non-B hepatitis. Clinically, type A and non-A, non-B hepatitis were indistinguishable; one case of fulminant disease occurred in each group. The type A cases were more frequent in young adults; non-A, non-B disease predominated in women 35 years or older. Epidemiologic backgrounds were generally similar, including illicit self-injection; but four transfusion-associated cases were limited to the non-A, non-B group. We conclude that relatively few HBsG-negative cases are due to hepatitis B virus, and that hepatitis A virus and non-A, non-B viruses are both important in acute non-B disease. [ABSTRACT FROM AUTHOR]