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Biomedical subjects

U Hopf

Publications and source records attributed to U Hopf.

At least 145 records · Page 8Linked to original sources
PubMed1979

LM-Ag and LSP--two different target antigens involved in the immunopathogenesis of chronic active hepatitis?

Two different types of immune reactions against liver membrane antigens have been described: firstly, cell-mediated immunity and autoantibodies against the liver-specific protein (LSP) in HBsAg-negative and HBsAg-positive chronic active hepatitis (CAH), and secondly, a liver membrane autoantibody (LMA) in HBsAg-negative CAH. Using 100,000 g supernatants of human and rabbit liver homogenates, the corresponding antigen of LMA could be separated by affinity chromatography on insolubilized LMA-positive sera from patients with HBsAg-negative CAH. A further characterization by crossed immunoelectrophoresis showed that LMA is directed against a soluble liver membrane antigen (LM-Ag) that is not a constituent of the purified LSP. LM-Ag seems to be species-unspecific and moves faster than LSP and serum albumin in crossed immunoelectrophoresis. While LSP is believed to be involved in the pathogenesis of HBsAg-negative and HBsAg-positive chronic active hepatitis, LM-Ag may be a target antigen only in cases of HBsAg-negative autoimmune CAH.

Antigens↗
PubMed1978

In vivo and in vitro binding of IgA to the plasma membrane of hepatocytes.

IgA bound in vivo was shown by immunofluorescence on the plasma membrane of isolated hepatocytes from subjects with normal liver and patients with liver cirrhosis, chronic active hepatitis or fatty liver. IgA in sera with elevated IgA concentrations, especially from cases with alcoholic cirrhosis, was bound in vitro to isolated hepatocytes from rabbit and mouse. This was not due to the high IgA concentration per se. Moreover, polyclonal polymeric serum-type and secretory IgA, and three of ten polymeric monoclonal IgA preparations, showed similar binding properties. Conversely, purified polyclonal and monoclonal monemeric IgA did not show affinity for the hepatocytes. The binding of polymeric IgA did not seem to depend on the proportion of dimers and larger polymers, kappa- or lambda-type light chains, heavy-chain subclasses, content of J chain or affinity for secetory component. The in vivo binding of IgA by hepatocytes is probably a physiological phenomenon which in part may explain the normal clearance of polymeric IgA from serum.

Binding Sites, Antibody↗
PubMed1978

[Circulating immune complexes in acute viral hepatitis, chronic active hepatitis, and periarteritis nodosa (author's transl)].

Circulating immune complexes were determined in patients with acute viral hepatitis, chronic active hepatitis and periarteriitis nodosa with the Raji cell technique. Circulating immune complexes were found in 11/18 HBsAg positive and HBsAg negative cases of acute viral hepatitis. In HBsAg positive chronic active hepatitis immune complexes were detectable in 42/43 cases but only in 1/27 HBsAg negative cases. Ten healthy HBsAg carriers demonstrated no detectable immune complexes. Using FITC conjugated antisera against HBs, HBc, and e antigen, immune complexes could not be found in any case of acute viral hepatitis or chronic active hepatitis. Elution of immune complexes from Raji demonstrated IgG, C'3 and a lack of HBsAg, HBc or e antigen. Immune complexes were present in 4/8 cases with periarteriitis nodosa. Viral components were detectable in one case.

Acute Disease↗
PubMed1978

Diagnosis of autoimmune chronic active hepatitis a simplified method for the detection of liver membrane autoantibodies (LMA).

A simplified method for the detection of liver membrane autoantibodies (LMA) in patient's serum is presented. Hepatocytes are isolated from the liver of young rabbits. A calcium-free solution without enzymes is injected into the portal vein with a normal syringe. The liver is then cut into small pieces in a solution with calcium, shaken in a water bath, filtered and washed in Eagle's medium. The isolated hepatocytes are incubated first in patient's serum and secondly in FITC labeled antihuman IgG. The test requires three hours and allow the detection of LMA, antinuclear and antimitochondrial antibodies simultaneously. The detection of LMA is valuable in the diagnosis of autoimmune chronic active hepatitis.

Animals↗
PubMed1978

[Circulating immune complexes and in vivo fixation of immunoglobulin G, A and C3 onto hepatocytes in patients with Crohn's disease (author's transl)].

In vivo fixation of immunoglobulin and C3 onto the hepatocellular membrane of patients with Crohn's disease was studied by immunofluorescence. IgG binding was observed in 93% of patients with disease activity but not in patients without disease activity. C3 binding was present in 21% of patients with active disease. IgA binding was found in approximately one half of all patients with Crohn's disease irrespective of disease activity. The immunoglobulin and C3 binding to hepatocytes was not correlated with histopathological findings. Circulating immune complexes were detected with the Raji cell assay in approximately one half of all patients with Crohn's disease and showed no correlation to disease activity. The following conclusions can be derived from these studies: 1. The in vivo fixed IgG represents immune complexes, which is eliminated by the liver as part of the physiological clearance function. 2. These aggregates bind to hepatocytes predominantly via IgGFc receptors. 3. Hepatocellular bound IgG and C3 show no correlation to histopathological liver alterations. 4. In vivo bound hepatocellular IgG aggregates have different properties than the immune complexes detected by the Raji cell assay.

Adolescent↗
PubMed1977

Liver-cell-membrane autoantibody specific for inflammatory liver diseases.

With an immunofluorescence technique using rabbit hepatocytes isolated by a non-enzymatic method an autoantibody directed against liver-cell-membrance was identified. Sera from 361 patients with various liver diseases and 274 patients with primary non-hepatic diseases-many associated with non-organ-specific auto-antibodies-were examined. The antibody (LMA) was found in 27 out of 72 patients with hepatitis-B-surgace antigen (HBsAg)-negative chronic active hepatitis and in 17 out of 28 patients with HBsAg-negative non-alcoholic cirrhosis. Only two patients had LMA and HBsAg, and both had chronic active hepatitis. One patient with extrhepatic disease was found to have LMA, and this patient had biochemical evidence of liver disease. Hence there is a close correlation between the presence of LMA and HBsAg-negative chronic inflammatory liver diseases and its detection may help in diagnosis.

Adult↗
PubMed1976

[Histocompatibility-(HLA) antigens in patients with HBsAg positive and negative hepatitis and healthy carriers of HBsAg and anti-HBs. (author's transl)].

New own data and a survey of published data concerning the frequencies of 23 HLA antigens in patients with HBsAg positive and negative chronic active hepatitis (CAH) and healthy carriers of Hepatitis-surface antigen (HBsAg) and high titers of antibodies to HBaAg (Anti-HBs) allow to conclude as follows: 1. Patients with CAH and persistence of HBsAg show a normal frequency of HLA-B8. 2. There is no increased frequency of HLA-B8 in HBsAg negative CAH without autoimmune antibodies. 3. Only in patients with HBsAg negative CAH with autoimmune antibodies is the frequency of HLA-B8 is statistically significantly increased (p less than 0.01 after correction for the number of antigens and different groups of patients compared). These are patients with the autoimmune form of CAH. 4. There exist no significant differences in the frequencies of the HLA antigens tested in patients with HBsAg positive CAH and healthy carriers of HBsAg and Anti-HBs. Thus no indications could be found for HLA-associated factors in the different behaviour to the hepatitis-B virus.

Adult↗
PubMed1976

[Humoral immune reactions on the hepatocellular plasma membrane in the experimental chronic active hepatitis in rabbits (author's transl)].

For the induction of experimental chronic active hepatitis (CAH) in rabbits long term immunization was performed with human liver-specific protein plus complete Freunds adjuvants. Serum antibodies against allogeneic hepatocellular membrane antigens could be detected after 23 weeks using isolated normal rabbit hepatocytes or by the passive hemagglutination technique with liver-specific membrane protein as antigen. Isolated hepatocytes from these rabbits showed in vivo fixed IgG on their plasma membranes in a linear and granular fluorescence pattern. Furthermore immune complexes (Raji-cell test) were detectable in the sera of these animals. After 23 weeks 3 out of 16 animals had developed a chronic active hepatitis (CAH). After 44 weeks 10 of 15 animals and after 78 weeks 6 of 7 surviving animals had a CAH. All these 7 animals had serum antibodies against membrane antigens of isolated rabbit hepatocytes and in vivo fixed IgG on their hepatocellular plasma membranes. The results suggest the existence of autoantibodies against hepatocellular membrane antigens. In addition, immune complexes may be bound to the plasma membranes. The pathogenetic role of these humoral immune reactions has yet to be determined.

Animals↗
PubMed1976

Detection of a liver-membrane autoantibody in HBsAg-negative chronic active hepatitis.

Investigation of humoral immunity against hepatocellular membrane antigens in patients with chronic active hepatitis and other liver diseases showed two different immunofluorescence patterns of IgG on hepatocyte membranes. A linear pattern was seen in HBsAg-negative hepatitis, but HBsAg-positive cases and some of protracted, acute hepatitis B had a granular pattern. In patients with IgG bound to hepatocytes, continuing necrosis of parenchymal liver cells was seen. Conversely, hepatocytes without bound IgG were found in cases of chronic active hepatitis in remission, acute viral hepatitis without HBsAg and chronic persistent hepatitis, in "healthy" HBsAg-carriers and in patients with fatty liver or alcoholic cirrhosis. A liver-membrane autoantibody in serum, proved by fixation on membranes of isolated rabbit hepatocytes, could be demonstrated only in HBsAg-negative chronic active hepatitis with elevated IgG-concentrations. The results support the existence of different pathogenetic types of chronic active hepatitis, a so-called autoimmune type and a hepatitis virus-B-induced type.

Acute Disease↗
PubMed1976

Demonstration of binding sites for IgG Fc and the third complement component (C3) on isolated hepatocytes.

Isolated hepatocytes from rabbits with experimental acute serum sickness showed immune complexes bound to the hepatocellular membrane with a coarse granular fluorescent pattern. Also in vitro preformed immune complexes (BSA-anti-BSA) or aggregated gamma-globulin from human and rabbit could be bound to the surface of isolated hepatocytes. In contrast, immune complexes with F(ab')2 anti-BSA were not fixed on the membranes. Hepatocytes incubated in fresh serum showed membrane-fixed C3 in a coarse granular pattern. This deposition could be abolished by heating (56 degrees C, 30 min) the serum or by adding EDTA (0.02 M). Also, purified human or guinea pig C3 could be bound to the hepatocellular membrane but in a linear fluorescent pattern. Thus, fixation of immune complexes on hepatocytes appears to operate through binding sites for IgG Fc and, possibly, also through binding sites for C3. It is suggested that these hepatocellular-binding sites may have a physiologic clearance function. In vivo fixed IgA could be detected on the membranes of isolated hepatocytes from healthy persons. It is assumed that the membrane-fixed IgA has a carrier function for antigens from the gut.

Animals↗