The clinical significance of the delta antigen-antibody system in hepatitis B infections.
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Animals↗
Biomedical subjects
M Rizzetto
Publications and source records attributed to M Rizzetto.
Radioimmunoassay detection of IgM antibodies to the hepatitis B core antigen in HBsAg liver disease.
A radioimmunoassay is described for detection of IgM antibody to the hepatitis B core antigen. The assay is based on the selective absorption of IgM immunoglobulins from test serum by anti-IgM fixed on a solid phase, followed by incubation with HBcAg and radiolabeled anti-HBc of IgG type. IgM anti-HBc was found in high titers in all the patients with acute hepatitis B; in two of four patients whose acute hepatitis progressed to chronicity, IgM anti- HBc disappeared in 4-6 months despite continuing HB viremia. IgM anti-HBc was also found in low titers in 19% of the patients with chronic HBV infection. No relation was noted between the presence of IgM anti-HBc and clinical or serological categories of chronic carriers of the HBsAg. The antibody was not found in carriers with hepatitis caused by superinfection with the hepatitis A virus or the HBV-associated delta agent. IgM anti-HBc is a marker of a recent HBV infection. Its absence in HBsAg-positive individuals with acute hepatitis should rise suspicion that the patients are carriers of the HBsAg experiencing disease caused by factors other than the HBV.
Antibodies, Anti-Idiotypic↗
Enzyme-linked immunosorbent assay for detection of antibody to the hepatitis B surface antigen-associated delta antigen.
A blocking enzyme-linked immunosorbent assay (ELISA) was developed for specific detection of antibody to the hepatitis B surface antigen-associated delta antigen. The sensitivity of ELISA was intermediate between that of previously described immunofluorescence and radioimmunological assays for anti-delta. Performance of ELISA was simple and required only ordinary and inexpensive laboratory equipment.
Antibodies, Viral↗
A radioimmunoassay for HBcAg in the sera of HBsAg carriers: serum HBcAg, liver HBcAg immunofluorescence as markers of chronic liver disease.
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Carrier State↗
Infection with the delta agent in chronic HBsAg carriers.
To establish the mechanism of progression to chronicity of the HBsAg-associated delta infection, serum hepatitis B virus and delta markers were tested in five babies born to HBsAg-positive mothers with anti-delta, in 42 follow-up patients with acute hepatitis B virus and delta hepatitis, and in collections of sera from 8 HBsAg carriers with anti-delta. Evidence of delta infection was found in the baby born to a mother with serum HBeAg and in none of the four babies born to mothers with anti-HBe. Hepatitis was self-limited in the 42 patients acutely infected by hepatitis B virus and delta agent; none developed persistent HBs-antigenemia and the majority displayed transient anti-delta of IgM class. In seven HBsAg carriers high titers of anti-delta developed during the follow-up; coincident with the rise of the antibody, aminotransferase elevation occurred in five previously asymptomatic carriers and persisted in three of them. No sign of infectious hepatitis B virus replication was detected in five of the carriers throughout the follow-up, and all of them had anti-HBe before the rise of anti-delta and of aminotransferase. HBsAg carriers with diminished hepatitis B virus synthesis appear to be at high risk of developing chronic delta infection and disease when exposed to the delta-infectious serum of other carriers.
Adult↗
Epidemiology of HBV-associated delta agent: geographical distribution of anti-delta and prevalence in polytransfused HBsAg carriers.
The epidemiology of infection with the hepatis-B-virus (HBV)-associated delta agent was assessed from the prevalence of antibody to delta in 1206 HBsAg-seropositive subjects from various parts of the world. Anti-delta was prevalent in unselected HBsAg-positive Italians, whether residents in Italy or elsewhere, and in drug addicts and polytransfused HBsag carriers throughout the world, suggesting that delta-associated infection is spread through contact in Italy and parenterally in other countries. Parenteral transmission of the delta agent was confirmed by a separate survey of the prevalence of anti-delta in 648 polytransfused patients with chronic blood disorders, which showed a higher prevalence of anti-delta in HBsAg-positive haemophiliacs than in the general HBsAg-positive population of Italy, Germany, and the U.S.A. In view of the failure to detect delta in the absence of markers of HBV, the prevalence of anti-delta among polytransfused HBsAg carriers suggests that the delta-associated agent is transmitted by superinfection or coinfection of HBsAg carriers, the HBsAg carrier state possibly providing a rescue function to the superinfecting agent.
Carrier State↗
delta Agent: association of delta antigen with hepatitis B surface antigen and RNA in serum of delta-infected chimpanzees.
The hepatitis B virus-associated beta antigen was found in the serum of experimentally infected chimpanzee as an internal component of a discrete subpopulation of hepatitis B surface antigen (HBsAg) particles. The 35- to 37-nm particles banded in CsCl at 1.24-1.25 g/cm3 and sedimented with a mobility intermediate between that of the hepatitis B virion and that of the 22-nm form of HBsAg. The particles contained only indistinct internal structure by electron microscopy and were not unique to delta agent infection, similar particles without delta-antigen activity being observed in the preinfection serum of HBsAg carrier chimpanzees. A small RNA (Mr, 5 X 10(5)) was temporally associated with delta antigen in the serum of infected chimpanzees and copurified with the delta-antigen-associated particles. This RNA is smaller than the genomes of known RNA viruses but larger than the viroids of higher plants.
Animals↗
Transmission of the hepatitis B virus-associated delta antigen to chimpanzees.
Inoculation of hepatitis B surface antigen (HBsAg)-positive sera from patients with chronic liver disease and intrahepatic delta (delta) into chimpanzees susceptible to infection with hepatitis B virus (HBV) resulted in type B hepatitis and delta markers (delta antigen and antibody to delta) in recipient animals. A dilution (10(-8)) of serum induced type B hepatitis without delta markers in another HBV-susceptible animal. HBV infection and delta markers did not develop in animals with preexisting titers of antibody of HBsAg. In chimpanzees with circulating HBsAg at the time of inoculation, synthesis of delta occurred earlier and its extent and duration were greater than in animals previously unexposed to HBV; coincident with synthesis of delta, hepatitis occurred in chronic HBsAg carriers, and synthesis of preexisting HBV gene products (HBsAg and hepatitis B core antigen) was diminished. Delta appears to be a marker of a transmissible pathogenic agent, either an HBV variant or another agent that requires the helper functions of HBV, that is defective and interferes with HBV replication.
Animals↗
The hepatitis B virus-associated delta antigen: isolation from liver, development of solid-phase radioimmunoassays for delta antigen and anti-delta and partial characterization of delta antigen.
The delta antigen-antibody (delta Ag/anti-delta) system is associated with type B hepatitis in man. The delta Ag was extracted and solubilized by sonication and treatment with 6 M GuHCl from the nuclei of human liver obtained at autopsy of a delta-positive subject. A microtiter solid-phase radioimmunoassay was developed and used for the partial characterization of delta Ag. Equilibrium centrifugation, gel filtration and chemical and enzymatic treatments revealed delta Ag to be a protein of approximately 68,000 m.w. with a buoyant density of 1.28 g/cm3 in CsCl, stable to heat, acid, nucleases, and glycosidases, and inactivated by alkali and proteases. A standard preparation of delta Ag was used to develop a blocking solid-phase radioimmunoassay for anti-delta.
Antibodies, Viral↗
Incidence and significance of antibodies to delta antigen in hepatitis B virus infection.
A microtitre solid-phase blocking radioimmunoassay (RIA) for antibody to the hepatitis B virus (HBV)-associated delta antigen was specific and detected anti-delta antibody at dilutions of serum of up to 10(6). Analysis of sera from HBsAg-negative subjects and different categories of HBsAg carriers from different regions confirmed the association of anti-delta antibody with HBV infection. Anti-delta antibody was detected in persistently high titres in 19.1% and 2.6% of sera from patients with chronic hepatitis and symptomatic chronic carriers, respectively, and was not detected in the sera of HBsAg-negative controls. Anti-delta antibody appeared transiently and in low titres (less than 1:500) in 4.8% of sera from patients with acute type B hepatitis. The presence and persistence of anti-delta antibody seem to be associated with chronic HBV infection and the development of progressive liver damage.
Acute Disease↗
Normal lymphocyte interferon production in adult HBsAg-positive chronic active liver disease.
To challenge the hypothesis that interferon (IF) production in chronic hepatitis-B virus liver disease is defective, lymphocytes from 14 patients with chronic active liver disease (CALD); from nine patients with chronic inactive liver disease (CILD), and from six healthy chronic carriers (HCC) were stimulated by Newcastle Disease virus. The patients with CILD showed a weak IF response by comparison with the controls (P less than 0.0005), whereas IF production by CALD patients and the HCC did not statistically differ from IF production in the healthy hepatitis-B surface antigen negative subjects who served as controls. These results indicate that IF treatment of CALD does not rely on a completely proved background.
Adult↗
An ultrastructural and immunohistochemical study on the delta antigen associated with the hepatitis B virus.
Thirteen liver biopsies in which the delta antigen was detected by immunofluorescence were studied by electron microscopy and immune electron microscopy with peroxidase labelled IgG and F(ab1)2 fraction obtained from a human antiserum containing high-titre anti-delta antibodies. The findings were compared with those obtained in 11 HBcAg positive and in two HBsAg negative controls. Neither unique particulate morphology nor any HB virus ultrastructural component were visualised in the delta positive specimens; 20-23 nm naked core particles were observed in 10 of 11 biopsies displaying the HBcAg in immunofluorescence. Delta positive nuclei frequently contained dense round structures of diameter varying between 20 and 30 nm with a soft indistinct edge. These granules did not exhibit characteristic ultrastructural features which enabled them to be distinguished from other granular material observed occasionally in nuclei of normal and diseased livers. However, their association with the delta antigen has been proved by the deposition on identical structures of peroxidase labelled anti-delta antibody. These results suggest that the delta antigen is unrelated to the Dane particle, the putative HB virus. The granules observed in the delta positive nuclei are composed of an amorphous matrix, possibly insoluble aggregates of the delta antigen.
Cell Nucleus↗
[Immunological study of carriers of Australia antigen (HBsAg)].
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Carrier State↗
An immunofluorescence blocking test to detect antibodies against the hepatitis B delta and core (HBcAg) antigens.
An immunofluorescence (IFL) blocking test has been developed to detect antibodies against the hepatitis B delta and core (HBcAg) antigens. The test proved useful to overcome the difficulties inherent in the detection of anti-delta by standard direct and indirect IFL procedures and provided a simple alternative to detect anti-HBc whenever serological techniques or indirect IFL, requiring purification of Dane particle cores or rare and selected HBcAg positive substrates, cannot be accomplished. The blocking test proved reliable and specific; though less sensitive than standard IFL techniques, it is simple and valuable in routine serological screening for anti-delta and anti-HBc.
Antibodies, Viral↗
[Stauffer's syndrome. Report of a clinical case].
The clinical case of a 52-year-old man with hypernephroma, abnormal hepatic function tests and no evidence of liver metastasis or abnormal histology is described. Liver function tests returned to normal values after nephrectomy. This case presents the features of the syndrome described by Stauffer in 1961 and can be added to the eighty or so cases reported since then.
Adenocarcinoma↗
Cell-mediated immunity to acetaldehyde in alcoholic liver disease demonstrated by leukocyte migration test.
To determine whether a sensitization to ethanol metabolites occurs in alcoholic liver disease, reactivity of lymphocytes to nontoxic amounts of acetaldehyde was studied by direct elaboration of migration inhibitory factor (MIF) production. Eighteen alcoholics with various degrees of biopsy-proven liver damage showed increased MIF production in response to acetaldehyde; the mean value of the group differed significantly from 15 healthy controls, 15 subjects with nonalcoholic liver disease, and 15 alcoholics without liver involvement (P less than 0.001, P less than 0.001, P less than 0.02, respectively). Among the alcoholics with liver disease, none individuals (50%) with histological signs of advanced alcoholic hepatitis showed the highest percentage of inhibition of migration; the value differed significantly from the remaining patients with lesser degrees of hyaline necrosis in liver biopsies (P less than 0.005). These results indicate that acetaldehyde is involved in the pathogenesis of alcoholic hepatitis. Clinically, this test might facilitate the selection of patients with alcoholic hyaline necrosis.
Acetaldehyde↗
Incidence and significance of different types of connective tissue antibodies in adult and pediatric gastroenterological disorders.
The incidence of connective tissue antibodies was assessed in 3,000 adults and in 388 pediatric patients with gastroenterological disorders. Following a previous classification, connective tissue antibodies were distinguished in 5 different types, R1 and R2 reacting with reticulin components, KC with Kupffer cells, AC and Rs with intra- and extracellular mesenchymal antigens. R1 predominated in children and was observed only in patients with malabsorption; the great majority of them had celiac disease and an abnormal small bowel mucosa. Ac was rarely seen in children and occurred in several unrelated gastrointestinal diseases of the adult; its incidence, however, was significantly higher in disorders with idiopathic and secondary malabsorption. R2, KC and Rs were seen only occasionally in unrelated gastroenterological disorders without malabsorption. R1, therefore, seems to be strongly suggestive of a malabsorption syndrome with abnormal small bowel mucosa and AC is a nonspecific reaction occuring predominantly in primary and secondary malabsorption; the other connective tissue antibodies have no clinical significance in gastroenterological disorders.
Adult↗
A counterimmunoelectrophoretic technique for the detection of HBeAg/anti-HBeAg (e antigen/antibody) in human sera.
A counterimmunoelectrophoretic technique is presented for the serological detection of the e system. Counterimmunoelectrophoresis was found reproducible and easy to perform; it is quicker and more sensitive than immunodiffusion since out of 243 HBSAg positive carriers, it detected HBeAg or anti-HBe in other 42 (17.3%) sera in addition to the 96 positive by immundiffusion.
Antibodies, Viral↗