Relapse after azathioprine withdrawal in autoimmune chronic active hepatitis.
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Autoimmune Diseases↗
Biomedical subjects
U Hopf
Publications and source records attributed to U Hopf.
[Serologic analysis of HBc antigen in patients with HBs-antigen carrier state].
Treatment of serum with sodium thiocyanate in HBs antigen carrier patients leads to liberation of circulating HBc antigen which can be demonstrated radioimmunologically. Investigations were done in 54 HBs antigen carriers, 44 of whom had chronic inflammatory liver disease (22 patients each HBe antigen positive and negative), and in 10 patients who were asymptomatic (so-called healthy HBs antigen carriers). Out of the 22 HBe antigen positive patients 17 were HBc antigen positive serologically. In the HBe antigen negative group of HBs antigen carriers two out of 22 patients with HBc antigen in serum were detected. All 10 asymptomatic HBs antigen carriers were HBc antigen negative. In 11 out of the 40 immunohistologically assessed patients HBc antigen could be demonstrated in hepatocellular nuclei; these 11 patients also demonstrated HBc antigen in serum. The liberated HBc antigen was associated with Dane particles in the density gradient. Serologic demonstration of HBc antigen may thus be considered as direct evidence of presence of hepatitis B virus.
Carrier State↗
[Binding activity of circulating HBsAg particles for polymerized human albumin in acute hepatitis B].
The binding activity of circulating HBsAg particles to polymerized human serum albumin (pHSA) was determined by radioimmunoassay in 18 patients with acute hepatitis B at follow-up and compared with other hepatitis B virus (HBV) markers. All patients had serum HBsAg particles with binding sites for pHSA during the acute phase of disease. Elimination of HBsAg particles with pHSA receptors occurred within 1 to 8 weeks in uncomplicated courses and in one case with a protracted course of 16 weeks before total elimination of HBsAg. The pHSA-test became negative after elimination of HBsAg in most instances. Three patients developed chronic hepatitis with persistence of pHSA-binding HBsAg particles. Circulating HBcAg dissociated by chaotropic ions was detectable in the first week of observation in 4 of 15 patients who recovered and persisted in 3 cases with transition to chronic disease. The results show that acute hepatitis B is associated with circulating pHSA-binding HBsAg particles which can serve as a prognostic marker of the early phase of the disease.
Adult↗
Hepatocellular clearance function of bacterial lipopolysaccharides and free lipid A in mice with endotoxic shock.
Hepatic uptake of bacterial lipopolysaccharides (LPS) in defined salt forms and free lipid A was studied in C3H mice. Extracts of 14C-labeled and unlabeled LPS from Salmonella abortus equi and lipid A from Salmonella minnesota R 595 (Re) were administered intravenously in doses sufficient to induce endotoxic shock. Sixty minutes after administration of 14C-LPS, 40% of the total activity was found in the liver tissue, 10% was in the isolated nonparenchymal cells, and only 1% was in the isolated hepatocytes. However, at this time only one third of the hepatocytes could be isolated; the other two thirds were obviously damaged. After 240 minutes, 55% of the total activity was measured in the liver tissue. The nonparenchymal cells had 8% of the activity, and all hepatocytes were damaged. By use of immunofluorescence, LPS S abortus equi was localized in sinusoidal cells 5 to 10 minutes after administration, and LPS S minnesota R 595 and lipid A were found in both nonparenchymal and parenchymal liver cells. All toxins were localized in both cell populations 60 and 240 minutes after injection. After application of LPS or lipid A, the third complement component (C3) was detectable in sinusoidal cells. In decomplemented mice the hepatic deposits of LPS and lipid A were unaffected, without demonstration of C3. The data indicate that LPS and lipid A interact in vivo with Kupffer cells and hepatocytes. Hepatic clearance of endotoxin seems to be independent of complement.
Animals↗
Binding activity of HBsAg particles from chronic HBsAg carriers to polystyrene beads coated with polymerized human serum albumin: diagnostic relevance of the assay.
The binding activity of HBsAg particles to polystyrene beads coated with polymerized human serum albumin (pHSA) was studied by radioimmunoassay in 48 patients with chronic HBsAg carrier state. The pHSA assay was positive in all 16 HBeAg-positive patients and in 22 HBeAg-negative HBsAg carriers with chronic hepatitis. Asymptomatic, "healthy" HBsAg carriers did not react in the pHSA assay. Mean binding activity was significantly higher in the HBeAg-positive group (P/N ratio 39.3) than in HBeAg-negative carriers with chronic hepatitis in various stages (P/N ratio 19.2). Fractionation of five representative HBeAg-positive sera by density gradient ultracentrifugation in cesium chloride yielded three peaks of HBsAg particles at 1.28, 1.22 and. 1.18 g/ml. The first HBsAg peak contained Dane particles and exhibited strong reactivity in pHSA assay. The second and third peaks, both consisting of 22 nm particles, reacted differently in pHSA assay. While about half of the HBsAg particles in the second peak were bound, reaction in the third HBsAg peak was predominantly negative. Intrahepatic HBsAg was detectable with the immunofluorescence technique in 19 of 22 HBsAg carriers. HBcAg was found in seven of 10 HBeAg-positive cases and in three of 16 HBeAg-negative patients with chronic hepatitis. The diagnostic value of pHSA assay might be seen in differentiation between HBeAg-negative chronic HBsAg carriers with liver disease or "healthy" carrier state.
Binding Sites, Antibody↗
[Immune thrombocytopenia in rectal cancer. Case report].
We report on a 72 year-old female patient, who presented with hemorrhagic purpura und rectal bleeding. A rectal carcinoma with local extension was confirmed by endoscopy. In addition the patient showed a considerable immune thrombocytopenia. Treatment with corticosteroids resulted in an increase in thrombocytes, but the steroids were discontinued because of diabetogenic side effects. Azathioprine had a transient effect on thrombocytopenia. The thrombocytes increased appreciably under intravenous application of gammaglobulin. The association between intestinal neoplasms and immune thrombocytopenia may be more frequent than assumed.
Aged↗
[Development of chronic active hepatitis of the autoimmune type following hepatitis B virus infection with HBSAg-persistence. 4 case reports].
Two female and two male patients aged of 26, 27, 36 and 46 years with HBsAg-positive chronic active hepatitis (CAH) are presented. The liver disease showed a marked progression with transition to cirrhosis in spite of seroconversion from HbeAg to Anti HBe in three cases. All four patients developed serological markers recognized as typical for the autoimmune type of CAH, such as hypergammaglobulinemia with appreciable elevation of IgG concentrations, antinuclear antibodies and liver membrane antibodies. Furthermore all four patients were positive for the histocompatibility antigen B8. These cases indicate that in genetically predisposed individuals hepatitis B viruses can induce autoimmune processes responsible for the progression of hepatic inflammation. In view of the therapeutic implications it is important to recognize patients with liver disease taking such a course.
Adult↗
[Immunologic parameters in pericholangitis and primary sclerosing cholangitis with and without ulcerative colitis].
Immunological parameters and histocompatibility antigens (HLA) were determined in seven patients with non-bacterial cholangitis. Four patients had pericholangitis and ulcerative colitis, three had primary sclerosing cholangitis, one of these with ulcerative colitis. All 7 patients had antinuclear antibodies; however, there were no antibodies against DNA, against mitochondria or liver membrane antigens. One patient had low-titre rheuma factors. Immunoglobulins G, A and M and complement components C3 and C4 were mostly in the normal range. HLA constellation was positive for B8 in 6 patients. These were male patients with disease manifestations between the 12th and 45th year of life. The results support the concept that pericholangitis and primary sclerosing cholangitis with or without ulcerative colitis are related hepatological disease entities with an immunological pathogenesis and an underlying genetical determination.
Adult↗
[Humoral autoimmune phenomena during long-term lithium treatment with special reference to thyroid autoantibodies].
In a retrospective study, 58 outpatients under long-term therapy with lithium were examined with regard to humoral autoantibodies. Fifty-five schizophrenic outpatients under neuroleptic treatment served as controls. We examined antithyroidal antibodies (TAK, MAK), smooth muscle antibodies (SMA), antimitochondrial antibodies (AMA), and antinuclear antibodies (ANA). In the lithium group there was a significant higher prevalence of antithyroidal antibodies (33%) as compared to the control group (9%). Ten patients out of 19 patients with antithyroidal antibodies showed MAK as well as TAK; moreover we found a characteristic pattern: MAK greater than or equal to TAK. All lithium-treated patients were euthyroid. Five patients out of the group with antithyroidal antibodies had goiter, three showed temporarily elevated serum concentrations of basal thyroid-stimulating hormone (TSH). We did not find such elevated levels of TSH in the group of eight patients with goiter but without antithyroidal antibodies. There was neither a correlation between the examined parameters and the lithium serum concentration nor the additional psychotropic medication. Our results indicate a significant higher prevalence of antithyroidal antibodies under long-term therapy with lithium as compared to a psychiatric control group. We do not consider these autoimmune phenomena as relevant pathogenetic factors.
Adult↗
Demonstration of circulating autoantibodies against the plasma membrane of isolated thyroid cells in Graves' disease.
Antibodies against the plasma membrane of isolated human and porcine thyroid cells were demonstrable by a linear fluorescence pattern in sera from 29 out of 37 patients with Graves' disease. In 3 cases the antibodies reacted only with human thyroid cells. In a group of patients with Hashimoto's thyroiditis, 6 of 8 sera reacted with human thyroid cells in a granular fluorescence pattern. With one exception, sera from patients with non-toxic goiter showed no binding of IgG to thyroid cells. Sera from healthy controls were negative in this test system. There was no correlation between the presence of antibodies against thyroid cells and antibodies against thyroglobulin. Antibodies against thyroid microsomal antigens were found in 80% of patients with circulating thyroid cell membrane antibodies; 5 sera with membrane antibodies were negative for microsomal antibodies. Twenty sera of patients with Graves' disease were tested by passive haemagglutination test against peak I and peak II of the human thyroid fractionation with Sephadex G100. Antibodies against peak I were found in 14 sera and against peak II in all 20 sera. The data indicate that the antibodies in sera from patients with Graves' disease are directed mainly against a species-unspecific antigen of the plasma membrane from thyroid cells with a probable molecular weight between 4-7 S and are unrelated to thyroglobulin.
Animals↗
[The detection of apolipoproteins AI and B in the liver of patients with and without hyperlipoproteinemia (author's transl)].
Liver sections as well as isolated liver cells from 5 patients with a normal liver and normal serum lipids and patients with familial hyperlipoproteinemia type IIa (n=6), type IIb (n=11), type IV (n=13) and type V (n=2) were studied for the presence of apolipoprotein (apo) AI and B by immunofluorescence technique. At the time of liver biopsy the actual serum concentrations of HDL- and LDL-cholesterol and triglycerides were determined. In patients without metabolic disturbances apo AI was detectable in hepatocytes in 2 out of 5 cases. Apo B was not found in the liver of these patients. The non-parenchymal liver cells did not show depositions of apoproteins. In the group of 32 patients with hyperlipoproteinemia 6 cases showed in the liver apo AI and 2 cases apo B. The apoproteins exhibited a granular fluorescence pattern in the cytoplasm of hepatocytes. There was no correlation between the apoproteins in the liver and the degree of fat depositions in hepatocytes or the concentrations of serum lipids. The results indicate that the fat droplets in hepatocytes of patients with hyperlipoproteinemia represent lipid particles free of apoproteins. The lack of apoproteins in the liver with elevation of lipids in serum can be explained with a disturbed hepatic clearance function for lipoproteins.
Adult↗
[Significance of cellularly bound immunoglobulin G in chronic hepatitis induced by hepatitis B virus (author's transl)].
In vivo binding of immunoglobulin G was determined in hepatocytes of 15 patients, who suffered from hepatitis B virus induced chronic hepatitis. The incidence of hepatocytes containing immunoglobulin G bound in a granular pattern correlated positively with HBcAg within the nuclei and negatively with HBsAg in cytoplasma. The third component of complement could not be demonstrated in the hepatocytes. No correlation was found between the degree of immunoglobulin G fixation and inflammatory activity within the liver. It is suspected that immunoglobulins deposited as granula within the cell are identical with phagocytized immune complexes, which may be composed of HBcAg and anti-HBc.
Biopsy↗
In vivo uptake of immune complexes by parenchymal and nonparenchymal liver cells in mice.
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Animals↗
The liver specific protein: evidence for species-specific and non-species-specific determinants.
Liver specific protein (LSP) is known to be a macrolipoprotein of complete organ-specificity but without complete species-specificity. This membrane antigen is believed to play an important role in the pathogenesis of human and experimental chronic active hepatitis (CAH). In the present study, we investigated the species-crossreactivity of LSP by crossed immunoelectrophoresis, tandem crossed immunoelectrophoresis and fused rocket immunoelectrophoresis. With a sheep anti human LSP serum, two determinants of human LSP could be detected--one was found to be species-specific, the other crossreacted with rabbit, rat, swine and mouse LSP; no reaction was found with bovine and sheep LSP. A rabbit anti human LSP serum, after short term immunization, reacted only with a species-specific determinant of human LSP, no species-crossreactivity was observed. In contrast, rabbits with experimentally induced CAH, after longterm immunization with human LSP, had developed an autoantibody to rabbit LSP in addition to antibodies to the species-specific determinant of human LSP. Antibodies to the liver membrane antigen (LM-Ag) could not be detected. In conclusion human LSP contains a species-specific and a non-species-specific determinant. CAH in rabbits is induced by the loss of tolerance to the non-species-specific determinant.
Animals↗
[Induction and pathogenesis of chronic hepatitis experimentally induced in rabbits (author's transl)].
Studies of recent years have focussed on the immunopathogenesis of chronic liver diseases. Long-term immunization of rabbits with human liver proteins leads to liver lesions typical for human CAH. Delayed hypersensitivity against rabbit liver proteins, tested by skintest, correlated with the morphological changes of the liver. Circulating autoantibodies to liver specific protein, circulating immune complexes and IgG fixed in vivo to isolated hepatocytes could be observed before the liver lesions had developed histologically. The main target antigen in experimentally induced CAH seems to be an organ-specific but species-crossreacting macrolipoprotein with a molecular weight above 1 million, which is localized on the outer surface of the hepatocyte membrane. The liver specific protein (LSP) contains species-specific and non-species-specific determinants. Autoantibodies to non-species-specific determinants of LSP could only be detected in animals which had already developed CAH. Thus experimentally CAH in rabbits may be induced by the loss of tolerance to non-species-specific determinants of the LSP complex. Cell mediated and humoral immunity to LSP in man is found in HBsAg positive and HBsAg negative inflammatory liver diseases. Thus experimental CAH in rabbits seems to be a model for virus-induced and non-virus-induced chronic inflammatory liver diseases.
Animals↗
[Physiology and pathophysiology of the reticuloendothelial system of the liver (author's transl)].
The reticuloendothelial system of the liver includes endothelial cells, Kupffer cells, fat storing cells and pit cells. Kupffer cells have special surface structures, the so-called fuzzy coat and immunological receptors, which are responsible for phagocytotic activity. The physiological role of the hepatic reticuloendothelial system is clearing various substrates as for instance proteins and lipoproteins, hemoglobin, bilirubin, immune complexes, bacterial toxins, and certain circulating cells. The activity of the reticuloendothelial system can be influenced by blood flow velocity, by opsonins produced by the body itself, and by certain exogenous factors. The function of the reticuloendothelial system may be estimated by methods, which are dependent essentially upon hepatic clearance of intravenously applied, special substances.
Animals↗
Demonstration of circulating immune complexes in Graves' disease by the Raji cell technique and their relation to different thyroid autoantibodies.
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Adult↗