Relevance of immune mediated mechanisms in progressive alcoholic liver injury.
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Acetaldehyde↗
Biomedical subjects
S Vento
Publications and source records attributed to S Vento.
In vitro effect of TP-1 (a calf thymic extract) on suppressor T-cell function of patients with autoimmune chronic active hepatitis.
Concanavalin A-activated T-lymphocyte suppression of IgG production was found to be significantly impaired in patients with untreated active autoimmune chronic hepatitis when compared to normals or patients with inactive disease. When the dose-response effect of TP-1, a calf thymic extract, on in vitro suppressor cell activity was assessed, lymphocytes from six out of eight patients with previously reduced suppressor cell function showed a significant improvement, while over a similar range the suppressor cell activity of most normal controls declined. These results support the possibility that defective immunoregulation in patients with autoimmune chronic active hepatitis may be related to a deficiency in thymic hormone levels.
Adjuvants, Immunologic↗
Serial study of liver-directed autoantibodies and autoreactive T-lymphocytes in acute viral hepatitis B.
To explore the mechanisms underlying liver-directed autoimmune reactions in acute Hepatitis B Virus (HBV) infection, we followed five subjects who were identified in the early incubation phase (30-70 days before the first elevation of transaminases). We assessed serially cellular (using a T-lymphocyte migration inhibitory factor assay) and humoral (RIA) immunity to LSP (a macromolecular, liver-derived lipoprotein complex) and hepatic lectin (HL), the liver-specific receptor for desialylated glycoproteins, which appears to be a major target antigen for autoreactions in autoimmune chronic active hepatitis. Anti-LSP and anti-HL autoantibodies were found, at some stage during acute HBV infection, in 4/5 subjects, whereas cellular immunity to the same antigens was detected in only two patients. Sustained production of anti-HL antibodies was noted only in patients showing cellular immunity to this antigen and was apparently secondary to liver damage, whereas anti-LSP antibodies were first detected at the onset of liver injury when there was no evidence of T-cell immunity to the same antigenic complex. One explanation for this apparent dichotomy between cellular and humoral responses to LSP is that a helper T-cell response to the major envelope component of HBV, HBsAg, which precedes by 10-20 days the development of anti-LSP antibodies, promotes a humoral reaction to autoantigens contained in the LSP preparation, coexpressed with HBsAg, on the surface of infected hepatocytes.
Adolescent↗
Liver autoreactivity in acute virus A, B and non-A, non-B hepatitis.
As part of an investigation into the question of whether virus-induced autoreactivity might contribute to liver damage in viral hepatitis, serial studies (from onset through recovery) of circulating liver autoantibodies have been performed in patients with uncomplicated acute virus A (AVH-A), B (AVH-B) and non-A, non-B (AVH-NANB) hepatitis in whom the time of onset of symptoms could be precisely documented. One hundred and forty-four sera from 35 patients were tested by radioimmunoassay for autoantibodies against the liver-derived lipoprotein complex, LSP, and also against one of its constituents--the asialoglycoprotein receptor, known as hepatic lectin (HL). Anti-LSP antibodies were found in all 10 patients with AVH-A, in 17/18 with AVH-B and in 3/7 with AVH-NANB at titres that declined during recovery. Anti-HL antibodies were detected concurrently in 6 of the AVH-A patients and in 5 with AVH-B but on only 1 occasion in 1 patient with AVH-NANB. Transient cellular immunity to LSP, assayed by a T-lymphocyte migration inhibitory factor test, was detected in 4 of the 6 AVH-B patients tested, 2 of whom also showed concurrent reactivity to HL, but these cellular immune responses did not correlate with production of anti-LSP and/or anti-HL. The findings indicate that humoral immune responses to liver cell surface antigens are frequently triggered by hepatitis A and B viruses, possibly via induction of autoreactive, T-cell independent, liver antigen-specific B lymphocytes. These liver-specific autoreactions have the potential to contribute to hepatocellular damage in virus A and B hepatitis but it seems unlikely that autoimmunity plays a significant pathogenetic role in NANB viral infections.
Adult↗
Prospective study of cellular immunity to hepatitis-B-virus antigens from the early incubation phase of acute hepatitis B.
Cellular immunity to hepatitis-B-virus (HBV) antigens was followed prospectively in five patients who were identified in the early incubation phase of acute HBV infection, between 30 and 70 days before the onset of liver damage. Cellular immunity to pre-S antigens was the first detectable immune response, appearing 30 days before the first rise in serum aminotransferases in every case. T-cell sensitisation to HBcAg followed, with IgM anti-HBc appearing 10 days later. A cellular immune response to HBsAg was the last to appear, 10 days before the onset of liver damage. These cellular immune responses are the earliest host responses to the virus infection and could be critical in initiating and directing the processes of liver damage and viral clearance.
Acute Disease↗
T-cell inducers of suppressor lymphocytes control liver-directed autoreactivity.
The sensitisation of helper T cells of patients with autoimmune chronic active hepatitis to a liver-cell membrane-expressed asialoglycoprotein receptor protein is shown to be associated with a defect of T cells that specifically induce suppressor lymphocytes. These lymphocytes are found in an activated state in the peripheral blood of healthy people and may form part of an immunoregulatory network which actively prevents autoimmunity.
Adult↗
Cellular immunity to nucleocapsid and pre-S determinants in asymptomatic carriers of hepatitis B virus.
Previous studies of cellular immunity in asymptomatic HBV carriers have been limited to evaluation of responses to plasma-derived HBsAg preparations. We have explored the specificity of cellular immune responses to HBV antigens in these subjects using an indirect T-lymphocyte migration inhibitory factor assay and three antigen preparations (recombinant nucleocapsid antigen (HBcAg), plasma-derived HBsAg with or without pre-S2, and Saccharomyces cerevisiae-synthesized HBsAg without pre-S2 region). T cells from 10 asymptomatic chronic HBV carriers with normal liver function tests were responsive to nucleocapside determinants (mean migration index = 0.55 +/- SD 0.07) and to pre-S2-positive plasma-derived HBsAg (MI = 0.62 +/- 0.05). However, none responded to HBsAg devoid of pre-S2 sequences (MI = 0.98 +/- 0.04). In further experiments, T cells from three HBV carriers, cultured with six different HBsAg preparations, exhibited responsiveness only to those preparations containing significant pre-S2 activities. Our results show that T-cell immunity to nucleocapsid determinants of the virus and HBsAg in present in asymptomatic HBV carriers; the latter is restricted to antigenic preparations containing significant pre-S2 activities. Hence, T-cell immunity to pre-S determinants may not always be associated with HBV clearance.
Adolescent↗
Immunological aspects of chronic active hepatitis.
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Adolescent↗
Cell-mediated immunity and suppressor-T-cell defects to liver-derived antigens in families of patients with autoimmune chronic active hepatitis.
By means of an indirect T-lymphocyte migration inhibitory factor assay, T-cell sensitisation to the asialoglycoprotein receptor, a liver-specific protein on the surface of hepatocytes, was found in patients with autoimmune chronic active hepatitis (CAH) but not in healthy relatives or spouses. Cellular immunity to a liver-derived lipoprotein complex (LSP) which also contains the asialoglycoprotein receptor, and to which immune reactions have been previously demonstrated in patients with CAH, was also examined. In contrast to the findings with the purified asialoglycoprotein receptor, cell-mediated sensitisation to LSP was detected in all the patients and also in 24% of first-degree relatives and 27% of spouses, suggesting an environmental influence. There was a functional defect in suppressor T lymphocytes specific for liver-derived antigens in 50% of first-degree relatives and 43% of second-degree relatives, but in only 9% of spouses. This abnormality of immunoregulation may be genetically determined and crucial to the development of the disease.
Adult↗
T-lymphocyte sensitization to hepatocyte antigens in autoimmune chronic active hepatitis and primary biliary cirrhosis. Evidence for different underlying mechanisms and different antigenic determinants as targets.
Cultured with a liver-derived lipoprotein complex, T lymphocytes from 42 of 45 patients with autoimmune chronic active hepatitis generated migration inhibitory factor compared with 16 of 33 patients with primary biliary cirrhosis. Unlike T lymphocytes from patients with primary biliary cirrhosis, the T-cell reactivity of patients with chronic active hepatitis was always suppressed by T cells from normal subjects and, with two exceptions, by T cells from patients with primary biliary cirrhosis, even when these latter cells exhibited sensitization to this same antigen complex. Using a component of the whole complex, the asialoglycoprotein receptor as antigen, migration inhibitory factor was invariably released by T cells from patients with autoimmune chronic active hepatitis, but from only 2 of 8 patients with primary biliary cirrhosis sensitized to the whole complex. Thus, in autoimmune chronic active hepatitis, but not in primary biliary cirrhosis, the asialoglycoprotein receptor is invariably a target for cellular immune reactions and is associated with a suppressor T-cell defect for hepatocyte antigens.
Adolescent↗
[Direct immune response against hepatic antigens in patients with alpha-1-antitrypsin deficiency].
We have investigated the possible role of cell-mediated immunity in the pathogenesis of liver disease associated with alpha 1-antitrypsin (AAT) deficiency in 16 children with PiZZ phenotype, who presented with liver disease in infancy. Peripheral blood lymphocytes from 13 patients were incubated with autologous hepatocytes in a microcytotoxicity assay. There was a clear trend for cytotoxicity to increase with age and thus significantly increased cytotoxicity was found in four cases older than 2 years, while intermediate values were recorded in three children between 6 months and 2 years and normal values in children younger than 6 months. Fractionation of PBL into T and non-T-enriched subsets showed that both were involved in the cytotoxic reaction. A purified liver membrane lipoprotein preparation (LSP) inhibited both T and non-T-cell cytotoxicity suggesting that LSP is a major target antigen in this system. Sensitization to LSP was also present in 2 of the 3 children studied using a recently developed T-lymphocyte migration inhibitory factor (T-LIF) test. Control experiments performed in infants with neonatal hepatitis syndrome, but with normal Pi phenotype showed consistently increased cytotoxicity values. Cell-mediated immune reactions directed against autologous hepatocytes develop late in the course of the liver disease associated with AAT deficiency. While this reaction cannot be involved in the pathogenesis of the initial liver lesion, it may contribute to perpetuation of liver damage.
Antigens↗
Immune mechanisms in autoimmune chronic active hepatitis.
Autoimmune chronic active hepatitis is a disease of unknown aetiology in which a dense mononuclear cell infiltrate in the portal areas of the liver is associated with ongoing necrosis of periportal hepatocytes. The finding of autoantibodies in serum, an increased frequently of HLA B8 DR3, a female predominance, an association with autoimmune diseases and the histological features all suggest a role for immunological reactions in the pathogenesis. Various immunological reactions have been demonstrated in vitro which could be of relevance to pathogenesis, including antibodies in serum directed against antigens expressed on the liver cell membrane, antibody-dependent cell-mediated cytotoxicity for autologous hepatocytes. T cell sensitisation to undefined hepatocyte antigen(s) and both antigen- and non-antigen-specific suppressor T cell defects. However, it is still unclear how these various phenomena interact in vivo and further studies are required to clarify their exact role in pathogenesis.
Antibody-Dependent Cell Cytotoxicity↗
Antigen specific suppressor cell function in autoimmune chronic active hepatitis.
An indirect migration inhibition assay has been used to show that lymphocytes from 26 of 29 patients with autoimmune chronic active hepatitis (CAH) generated T lymphocyte migration inhibitory factors (T-LIF) in the presence of liver specific protein (LSP), compared with only 1 of 21 patients with HBsAg-positive chronic liver disease and none of 19 controls. Generation of T-LIF activity in response to LSP was not observed in any of 5 patients with autoimmune thyroid disease although their T lymphocytes did generate T-LIF activity in the presence of thyroid membrane antigens. T lymphocytes from 1 patient with autoimmune liver and thyroid disease generated T-LIF activity in the presence of both LSP and thyroid membrane antigens. The generation of T-LIF activity by T cells from autoimmune CAH patients was suppressed when these cells were co-cultured in a 9:1 ratio with T cells from normal subjects and patients with HBsAg-positive chronic liver disease, but was unaffected if co-cultured with T cells from other patients with autoimmune CAH. T cells from patients with autoimmune CAH did, however, suppress the generation of T-LIF activity by T lymphocytes from patients with autoimmune thyroid disease when these cells were cultured with thyroid membrane antigens. After pretreatment with cimetidine or mitomycin-C for 30 min, T cells from normal subjects lost their ability to inhibit the generation of T-LIF activity to T lymphocytes from autoimmune CAH patients. These results are consistent with the hypothesis that there exists a defect in the specific suppressor T cell population controlling the immune response to LSP in autoimmune CAH which is unaffected by disease activity and treatment and which may be of fundamental importance in the pathogenesis of the disease.
Adult↗
[Markers of viral hepatitis B. Diagnostic, prognostic and therapeutic relevance].
Analysis of the behaviour and chronological development of B virus markers (including those most recently identified) in acute and chronic hepatitis gives rise to a diagnostic hypothesis about their presence and association. The prognostic and therapeutic significance of the markers is also emphasised with particular reference to fulminating and chronic active HBSAg and D positive hepatitis and the early diagnosis of liver cell carcinoma.
Acute Disease↗
[Benign monoclonal gammopathies: probable antibody specificity of monoclonal immunoglobulins].
40 patients with benign paraproteinemia have been studied in relation to their age and associated diseases. Significantly high frequency of liver diseases (CALD, cirrhosis, hepatoma, metastases) has been found (12 over 40 people) and increased incidence of idiopathic paraproteinaemia in the old age has been confirmed. 9 patients have been followed for 5 years, so that one could be sure that they had really benign paraproteinaemia: these patients have been then studied from an immunological point of view, in vivo by means of skin tests (PPD, Candida, Trichophyton, DNCB) and in vitro by searching for circulating immune complexes (using a new highly specific immuno-enzymatic method), and compared to controls without paraproteinaemia. Highly positive skin tests have been found only in 7 over 9 patients (even in old subjects) and 6 of them had circulating immune complexes (C.I.C.) in their sera; all the controls were negative both for skin tests and for C.I.C. Immune complexes have been found also in some cases of idiopathic paraproteinaemia, so that they do not seem to be in relation to the associated diseases. The Authors suggest that a genetically determined defect in regulator/suppressor T lymphocyte activity may cause the growth of a benign B cell neoplasm; and that monoclonal immunoglobulins most probably have antibody specificity and are directed against target antigens.
Adult↗
[Are HBsAg positive viral hepatitis and its fate caused by the genetically determined immune response to the infection?].
The Authors, after a review of the latest researches about the immunopathogenesis of hepatitis B, propose a new hypothesis that points out the importance of antigen-specific suppressor T-lymphocyte activity for the evolution of hepatitis-B-virus infection. It is possible to verify this working hypothesis by employing a modified migration inhibition factor test, using preparations of isolated T-lymphocytes.
Antibodies, Viral↗
T lymphocyte sensitization to HBcAg and T cell-mediated unresponsiveness to HBsAg in hepatitis B virus-related chronic liver disease.
Using a newly developed indirect T lymphocyte migration inhibition test, cell-mediated immunity to HBsAg and HBcAg was directly and simultaneously examined in a total of 21 patients with HBsAg-positive chronic liver disease (CLD), and in seven subjects whose sera contained anti-HBs (2 previous acute hepatitis B; 4 hepatitis B vaccine recipients and 1 chronic active hepatitis). T cell sensitization to HBcAg was invariably detected in the HBsAg-positive CLD patients tested (12/12), whereas T cell sensitization to HBsAg was not present in any of the patients (0/21). In contrast, T cell sensitization to HBsAg was present in all anti-HBs-positive subjects. These results support the hypothesis that the cellular immune response to HBcAg, rather than to HBsAg, is implicated in the pathogenesis of HBsAg-positive CLD. Moreover, the observation that the addition of T cells from patients with HBsAg-positive CLD to T cells from anti-HBs positive subjects in a ratio of 1 to 9 reversed their sensitization to HBsAg, suggests that a hyperactivity of HBsAg-specific suppressor T cell population may be responsible for persistent HBs antigenemia.
Adult↗
The ParaSight-F rapid dipstick antigen capture assay for monitoring parasite clearance after drug treatment of Plasmodium falciparum malaria.
Three methods for the detection of Plasmodium falciparum infection in peripheral blood were compared during antimalarial treatment and follow-up in 32 Burundian patients: dipstick antigen capture assay, standard (TBF) and prolonged thick blood film examination (PTBF) (3 x 5 min and 3 x 20 min examination respectively). Parasitaemia was determined daily by comparison with total white blood cell counts (determined by Coulter counter) until no parasite was detected on 2 consecutive days by PTBF. Cumulatively, 231 observations were made with each assay: 64 were negative and 167 positive by PTBF (59 had parasite counts < or = 100/microL). Compared to PTBF, the sensitivities of TBF and the dipstick assay were 1.0 for parasite counts > 100/microL and 0.458 and 0.966 respectively for counts < or = 100/microL. Overall, the dipstick assay was significantly more sensitive (0.988 vs. 0.808; P < 0.001) but less specific (P = 0.013) than TBF. The dipstick assay is of potential use for monitoring response to drug treatment and for detecting low parasitaemias.
Adolescent↗