Hepatocellular expression of lymphocyte function—associated antigen 3 in chronic hepatitis

T lymphocyte-mediated cytolytic immune reactions are considered a major cause of hepatocyte injury in chronic viral and autoimmune hepatitis. To further investigate local immune responses, we studied the expression of lymphocyte antigens and cell-cell interaction molecules known to be involved in effector-target cell interactions by light and electron microscopy in liver biopsy specimens from patients with chronic viral and autoimmune hepatitis. CD8+ lymphocytes were found to be the predominant population of cells in the inflammatory infiltrate in chronic hepatitis B and non-A, non-B hepatitis. In contrast, CD4+ cells constituted a comparably higher proportion of cells and were more numerou…

Drug Treatment for Chronic Hepatitis C Infection and Cancer Risk

BACKGROUND In patients with chronic hepatitis C infection, a sustained virologic response (SVR) to interferon-based therapy markedly decreases the incidence of hepatocellular carcinoma (HCC) over the long term. This is also true for patients who have hepatic cirrhosis, as well as for those with HCC-with or without cirrhosis-who have undergone resection or ablation with curative intent. Recent publications, however, have reported a higher incidence of HCC among patients in both of these subgroups who were treated with direct antiviral agents (DAA) rather than interferon-based therapy. METHODS A selective search for pertinent literature was carried out in the PubMed database with the search t…

Automatische Detektion der primär sklerosierenden Cholangitis (PSC) anhand von 3D-MRCP Datensätzen mittels Deep Learning

Hepatitis C virus antibody secretion in vitro by peripheral blood lymphocytes.

A recombinant polypeptide corresponding to a virus-specific cDNA clone (c100-3) serves as the antigen for a hepatitis C virus (HCV) antibody assay. Previous investigations have shown an 80% prevalence of HCV antibodies in sera of patients suffering from post-transfusional chronic hepatitis non-A, non-B, but positive results were also obtained for 30 to 70% of sera from patients with chronic hepatitis B or autoimmune hepatitis. In this study we show that HCV antibodies are secreted by peripheral blood lymphocytes (PBL) in vitro. PBL from 12/35 patients with chronic non-A, non-B hepatitis and 1/6 patients with chronic active hepatitis B spontaneously secreted HCV antibodies in cell culture su…

PNPLA3 and HSD17B13 gene variants exert opposite effects on fatty liver phenotypes: results from the FLAG cohort

The significance of the pre-S region of the hepatitis B virus

Hepatitis C virus (HCV) and autoimmune liver diseases

Anti-HCV tests were positive in 18–45% of sera from patients with autoimmune chronic active hepatitis. High gammaglobulin levels may result in false positive results, however, some sera show true positivity. PCR testing of such sera is necessary in order to determine whether HCV is directly involved in specific forms of the disease.

Clinical significance of the polymerase chain reaction (PCR) assay in chronic HBV carriers

PCR was evaluated as a clinical tool for use in accurate identification of the specific etiologic agent in chronic HBV carriers. The method was found to be valuable in diagnosis and for monitoring therapy, as well as for elucidation of genotypic variants of HBV in chronic HBV cases. By this means an HBV defective variant with alterations in the preSl/preS2 sequence was detected and is consequently described here.

Human immunodeficiency virus infection mimics autoimmune hepatitis--a case report.

A mitochondrial antigen-antibody system in cholestatic liver disease detected by radioimmunoassay.

A radioimmunoassay (RIA) was established for the detection of antimitochondrial autoantibodies (AMAs) in patient sera. AMAs were detected by RIA in 12 of 14 patients with primary biliary cirrhosis and in 3 of 29 patients with chronic active hepatitis. AMAs were detected by indirect immunofluorescence in all sera positive by RIA. In addition, two patients with primary biliary cirrhosis and one patient with chronic active hepatitis were AMA positive when tested by indirect immunofluorescence, but negative when tested by RIA. AMAs were not detected by RIA or indirect immunofluorescence in 121 further patients with various hepatic and nonhepatic diseases, including healthy controls. The RIA det…

Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibody-positive autoimmune chronic active hepatitis

SUMMARY Autoantibodies against microsomal antigen of liver and kidney (LKM-1) are diagnostic markers for a subgroup of autoimmune chronic active hepatitis (AI-CAH). Cytochrome P4S0dbl, now classified as cytochrome P450 IID6, is the major antigen of LKM-1 antibodies. Immunohistological studies suggest that hepatic injury in AI-CAH is mediated by liver-infiltrating T cells. In the present study the specificity and function of liver-infiltrating T cells was analysed at the clonal level. Phenotypical characterization of 189 T cell clones isolated from four liver biopsies of LKM-1 antibody-positive patients showed an enrichment of CD4+CD8- T cells. Five CD4+CD8- T cell clones proliferated specif…

Serum hyaluronate and type III procollagen aminoterminal propeptide concentration in chronic liver disease. Relationship to cirrhosis and disease activity.

. To analyse the relationship between the presence of liver cirrhosis and hepatic inflammation and the serum concentrations of the aminoterminal propeptide of procollagen type III (P-III-NP) and of hyaluronic acid (HA) in chronic liver disease, we measured P-III-NP and HA concentrations in paired serum samples from 133 patients with various chronic liver diseases, from 22 patients with acute hepatitis and from 50 healthy age-matched controls. In 24 (of the 133) patients with autoimmune chronic liver disease, follow-up determination was performed during therapeutic treatment with immunosuppressive drugs. Compared with controls P-III-NP concentrations (medians) were significantly elevated in …

Autoreactive liver-infiltrating T cells in primary biliary cirrhosis recognize inner mitochondrial epitopes and the pyruvate dehydrogenase complex.

Primary biliary cirrhosis (PBC) is characterized by lymphoid infiltrates in the portal tracts of the liver and the occurrence of antimitochondrial autoantibodies in serum directed against components of the pyruvate dehydrogenase complex and the other alpha-keto acid dehydrogenase complexes. These enzymes are located on the inner mitochondrial membrane. The destruction of the biliary tract in PBC is thought to be mediated by autoreactive liver-infiltrating T cells exerting cytotoxic activity or releasing certain lymphokines. In this study the reactivity of liver infiltrating T cells was shown to a bovine pyruvate dehydrogenase complex (PDH), a purified E2 subunit (PDH-E2) and a crude prepara…

Effects of the common PNPLA3 p.I148 M polymorphism on the fatty liver phenotypes in German patients: results from the FLAG “real life” cohort

T cell receptor gene rearrangements of T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis (PBC): Oligoclonality of PBC-derived T cell clones

Immunological events are involved in the pathophysiology of chronic active hepatitis as indicated from the accumulation of T lymphocytes at the site of tissue damage. We generated T cell clones from liver biopsies of 3 patients with chronic active hepatitis B and 2 patients with primary biliary cirrhosis. These T cell clones (n = 84) were analyzed by means of T cell receptor (TcR) beta gene rearrangements to determine whether the infiltrate consists of a polyclonal or oligoclonal T cell population. The vast majority (62 of 64) of T cell clones from three different patients with chronic active hepatitis B showed no identical rearrangements of the TcR beta chain genes. In marked contrast, in …

Antibodies to cytoskeletal proteins in patients with Crohn's disease

. The immunologic basis of inflammatory bowel disease has been the focus of interest of a series of studies on Crohn's disease and the process of immune sensitization at the gastrointestinal mucosal level is functionally poorly understood. To date only few contradictory reports concerning the incidence of autoantibodies in patients with this disease exist. The aim of this study was to investigate the sera drawn from 60 patients suffering from biopsy-proven Crohn's disease to evaluate the prevalence of autoantibodies against nuclear antigens and cytoskeletal proteins. Using standard methods, no anti-nuclear antibodies or antibodies to extractable nuclear antigens could be detected. All sera …

In vitro production of anti-neutrophilocyte-cytoplasm-antibodies (ANCA) by Epstein-Barr virus-transformed B-cell lines in Wegener's granulomatosis.

The frequent detection of anti-neutrophilocyte-cytoplasm-antibodies (ANCA) in patients with Wegener's granulomatosis (WG) led to the supposition that this disease might be of autoimmune nature. For some authors assume that Epstein-Barr virus (EBV) infection of human B-lymphocytes besides polyclonal activation could reveal the cryptic immune status against different autoantigens in patients with autoimmune diseases we investigated EBV-transformed B-lymphocytes from patients with Sjögren's syndrome, mixed connective tissue disease, WG and healthy blood donors. Two stable B-cell lines (Ho3, We1) could be established. Inhibition experiments showed that antibodies produced by transformed B-lymph…

Membrane Expression of Autoantigens on Mechanically and Enzymatically Isolated Hepatocytes

Die Plasmamembranexpression von Leberzellmembran-Antigenen wurde mit indirekter Immunfluoreszenz (IF) und Immunelektronenmikroskopie (IELMI) an mechanisch und enzymatisch isolierten Kaninchenhepatozyten untersucht. 90 – 95 % der enzymatisch isolierten Hepatozyten, aber nur 40 – 60 % der mechanisch isolierten Hepatozyten waren intakt und vital. Eine Untergruppe der autoimmunen chronisch aktiven Hepatitis (CAH) weist zirkulierende Antikorper gegen ein mikrosomales Antigen aus Leber und Niere (LKM) auf. Die vermutete Membranexpression fur LKM-Antigene konnte durch unsere Untersuchungen mit IF und IELMI an vitalen Kaninchenhepatozyten nicht nachgewiesen werden. Der als Referenzantikorper verwen…

Hepatic transferrin receptors in hereditary hemochromatosis.

Clonal analysis of human T lymphocytes infiltrating the liver in chronic active hepatitis B and primary biliary cirrhosis

Human T lymphocytes infiltrating the liver in chronic active hepatitis B (CAH-B) and primary biliary cirrhosis were isolated from liver biopsy cores, cloned by limiting dilution technique and expanded in vitro. Phenotypic and functional analysis demonstrates that this tissue infiltrate represents a heterogeneous cell population. However, when compared to peripheral blood lymphocytes of the same patients, a marked enrichment for T8+ cytotoxic T cells was found to exist at a local site in both types of chronic liver disease. These data provide support for the notion that liver cell injury in CAH-B and PBC may be mediated by a common immunologic mechanism likely executed by cells of the T line…

Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study

PubMed: 29599078

Characterisation of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen.

Autoantibodies against a soluble liver antigen (SLA) were detected in 23 patients with HBsAg-negative chronic active hepatitis (CAH) but not in 502 patients with various other hepatic and non-hepatic disorders or 165 healthy blood donors. Anti-SLA-positive serum samples were negative for antinuclear and liver-kidney-microsomal antibodies, markers of two subgroups of autoimmune-type CAH, 6 anti-SLA-positive patients were negative for all autoantibodies sought. Most of the anti-SLA-positive patients were young women (2 men, 21 women; mean age 37 years) with hypergammaglobulinaemia (mean 3.2 g/l, range 1.8-5.3 g/l); 18 of the 23 patients had received immunosuppressive treatment and all respond…

Autoimmunity and liver disease

Obeticholic acid for the treatment of non-alcoholic steatohepatitis: interim analysis from a multicentre, randomised, placebo-controlled phase 3 trial.

© 2019 Elsevier Ltd. All rights reserved.

Two different subtypes of antimitochondrial antibodies are associated with primary biliary cirrhosis: identification and characterization by radioimmunoassay and immunoblotting.

Antimitochondrial antibodies from patients with primary biliary cirrhosis react with different mitochondrial polypeptides as demonstrated by Western blots. The IgG fractions of a patient with primary biliary cirrhosis Stage I reacting exclusively with a pair of polypeptides at 48,000 daltons (p 48) on Western blot and from a patient with Stage III primary biliary cirrhosis reacting exclusively with a single 62,000 dalton polypeptide (p 62) were labeled with 125I; two radio-immunoassays were established detecting antimitochondrial antibodies against p 62 and p 48, respectively. Autologous sera blocked the assay, but the two reference sera did not block each other. Fourteen of 40 patients wit…

ELISA techniques for the detection of antimitochondrial antibodies

Detection of mitochondrial antibodies directed against the primary biliary cirrhosis (M2) antigen by an enzyme-linked immunosorbent assay (ELISA)

An enzyme-linked immunosorbent assay (ELISA) was developed for the detection of 1 subtype of mitochondrial antibodies (AMA) specific for chronic cholestatic inflammatory liver diseases. AMA were detected by ELISA in 16 of 16 patients with primary biliary cirrhosis (PBC) and in 2 of 31 patients with chronic active hepatitis. These 18 positive sera were positive for AMA by indirect immunofluorescence (IF) and by radioimmunoassay (RIA). No AMA were detected by ELISA in 2 patients with the pseudolupus erythematosus syndrome, who were positive for AMA by IF, 2 patients with secondary syphilis, positive for cardiolipin antibodies, 1 patient with systemic lupus erythematosus, positive for AMA by I…

Liver membrane autoantibodies in chronic active hepatitis

Summary Target antigens relevant for immune reactions in inflammatory liver diseases should be expressed on the hepatocellular membrane. Using mechanically or enzymatically isolated rabbit hepatocytes, we evaluated the influence of cell integrity on the detection of membrane-expressed antigens by sera from patients with chronic hepatitis and by murine monoclonal antibodies. Our results provide evidence that target antigens of liver membrane autoantibodies (LMA) as well as liver kidney microsomal antibodies (LKM) are not expressed on the hepatocellular membrane of viable and intact isolated rabbit hepatocytes. However, LMA were detected in the sera of 56% of patients with autoimmune chronic …

Treatment of chronic type B hepatitis with recombinant alpha-interferon induces autoantibodies not specific for autoimmune chronic hepatitis.

Recombinant human alpha-interferon is now under intensive investigation as therapy for chronic Type B hepatitis. Recent reports have suggested that prolonged alpha-interferon therapy may induce autoimmune reactions. We have evaluated the problem of autoimmunity related to alpha-interferon therapy by testing for 15 different antibodies in the sera of 31 patients treated with alpha-interferon. No patient had autoantibodies before treatment; 27 (87%) of 31 patients developed at least one autoantibody. Eleven patients had antinuclear antibodies and 21 had smooth muscle antibodies, both of which usually developed during alpha-interferon therapy. In contrast, antibodies to endocrine organs such a…

Analysis of liver-specific protein LSP using murine monoclonal antibodies.

. We describe twenty murine monoclonal antibodies directed against different antigenic determinants of human and rabbit liver-specific protein LSP. Among them, nine were directed against liver-specific epitopes as judged from immunohistological studies. Immunoelectronmicroscopy revealed that seven of these monoclonals recognized membrane determinants differing in staining of distinct areas of the hepatocellular surface. Eleven antibodies were directed against intracellular structures. Western blot analysis showed that the epitopes detected were displayed on either single or multiple protein bands with apparent molecular weights between 24 000 and 60 000. Further differences were observed wi…

Global prevalence and genotype distribution of hepatitis C virus infection in 2015:a modelling study

WOS: 000426979400014

Liver cell damage caused by monoclonal antibody against an organ-specific membrane antigen in vivo and in vitro

Summary Monoclonal antibodies have been raised against different antigenic determinants of normal rabbit hepatocytes. One antibody (2D3) recognized a liver-specific 43 kDa protein displayed exclusively on the basolateral portion of the hepatocellular membrane. Purified monoclonal antibodies were injected intravenously into rabits. Following the injection of antibody 2D3, a dose-dependent increase of liver enzyme activities in sera was observed. Within 8 h, marked morphological alterations of the hepatocytes, including multiple cell necroses, could be demonstrated by light and electron microscopy. When isolated vital rabbit hepatocytes in culture were used as targets, cytotoxic effects of th…

Liver-infiltrating T helper cells in autoimmune chronic active hepatitis stimulate the production of autoantibodies against the human asialoglycoprotein receptor in vitro.

SUMMARYAutoantibodies against the human asialoglycoprotein receptor (ASGPR) occur in the sera orpaticnts with autoimmune liver disorders. Live-nfiltrating T cell clones that specifically recognize the ASGPR have been described in patients with autoimmune chronic active hepatitis (A-AH) and primary biliary cirrhosis (PBC). Recently, we have shown that peripheral blood mononuclcar cells (PBMC) from patients with A-AH or PBC but not chronic viral hepatitis secreted ant-SGPR antibodies in vitro. In this study we characterized the influence of live-nfiltrating T cells on the secretion of ASGP-pecific autoantibodies by autologous B cells in cell culture supernatants. T cell clones from liver biop…

Chronic active hepatitis associated with vitiligo, nail dystrophy, alopecia and a new variant of LKM antibodies

In this report we describe the case of a 7-year-old boy, suffering from autoimmune-type chronic active hepatitis (AI-CAH) associated with vitiligo, nail dystrophy, alopecia areata and a variant of liver kidney microsomal (LKM) autoantibodies. This patient's antibodies are different from LKM-1 which are directed against cytochrome P450 db1. They react predominantly with perivenous hepatocytes in contrast to LKM-1 antibodies which homogeneously stain the whole liver lobule in immunofluorescence. In Western blot analysis this LKM variant reacts with a liver microsomal protein of approx. 50 kDa, but not with recombinant LKM-1 (cytochrome P450 db1) antigen. Immunosuppressive treatment led to a n…

Assay of hepatitis B virus DNA by polymerase chain reaction and its relationship to Pre-S- and S-encoded viral surface antigens

The polymerase chain reaction was evaluated as a diagnostic tool in 72 chronic hepatitis B virus carriers. Hepatitis B virus DNA was detectable in the serum of HBsAg—positive virus carriers using aliquots as small as 100 al. The detection limit for cloned hepatitis B virus DNA was 100 ag. Primer pairs for different regions of the HBV genome resulted in different sensitivity. Detection of the amplified hepatitis B virus DNA by Southern blotting and subsequent scintillation counting or densitometry allowed a semiquantitative assay. Using several primer pairs in parallel for optimal detection, all HBeAg-positive HBsAg carriers, 80% of HBe antibody—positive symptomatic HBsAg carriers and 57% of…

Characterization of liver cytokeratin as a major target antigen of anti-SLA antibodies.

Abstract Anti-SLA antibodies characterize a newly defined subgroup of patients with autoimmune chronic active hepatitis. The aim of the present study was the immunochemical characterization of the target antigen(s) of anti-SLA antibodies. Anti-SLA-positive sera were found to contain high titres of anti-cytokeratin antibodies. In immunoblotting analyses with 100 000 × g supernatants of human liver homogenates (S-100) these sera recognized various proteins with a molecular mass of 40–60 kDa. These proteins were also recognized by monoclonal anti-cytokeratin antibodies. Two-dimensional co-electrophoresis and immunoblotting analysis of S-100 and liver cytokeratins showed that anti-SLA antibodie…

Immune blot analysis of viral surface proteins in serum and liver of patients with chronic hepatitis B virus infection

The small and the middle surface proteins of hepatitis virus form either the virion or the 22 nm particle both of which are secreted. The large surface protein by itself remains cell bound in artificially transfected cell culture unless it is accompanied by an excess of the smaller protens. Its behavior in vivo is not yet well studied. Using specific monoclonal antibodies for immunoblotting, we found an abundance of small surface protein in the serum of chronic virus carriers and moderate amounts in the liver irrespective of viremia. The large surface protein was present in the serum and the liver of viremic carriers. In nonviremic carriers, the large protein was absent from serum, but in t…

Identification and characterization of a monoclonal antibody to the membrane fatty acid binding protein

A monoclonal antibody to the rat liver membrane fatty acid binding protein (MFABP) was prepared by immunizing mice with purified MFABP isolated from solubilized rat liver plasma membrane proteins by oleate-agarose affinity chromatography technique. The monoclonal antibody K15/6 identified a single 40 kDa protein in rat liver plasma membranes with pI values of 8.5, 8.8 and 9.0, which is identical to the authentic MFABP, but clearly distinct from rat mitochondrial GOT. The antibody K15/6 selectively inhibited cellular influx as well as membrane binding of fatty acids, but not of cholesterol or vitamin E. The same antibody was used in immunofluorescence, ELISA and Western blot analysis to dete…

The road map toward an hepatitis C virus-free transplant population

Antiviral therapy to eradicate hepatitis C virus (HCV) infection improves outcomes in patients undergoing liver transplantation (LT) for advanced chronic HCV with or without hepatocellular carcinoma. Traditionally, antiviral therapy focused on the use of interferon (IFN)-based regimens, with antiviral treatment initiated in the posttransplant period once recurrent HCV disease with fibrosis in the allograft was identified. The use of IFN-based therapy was limited in pretransplant patients with advanced liver disease. Earlier intervention, either before transplantation or early after LT, is now feasible with the advent of second-generation direct-acting antiviral agents (DAAs) with superior t…

PENTAZOCINE HAMPERS BILE FLOW

Prevalence of antibodies to hepatitis C virus among patients with cryptogenic chronic hepatitis and cirrhosis

Many cases of chronic hepatitis and cirrhosis cannot be attributed to a known cause and are collectively referred to as cryptogenic chronic liver disease. We have evaluated the role of the hepatitis C virus in the pathogenesis of this condition in a retrospective serum analysis for antibody to hepatitis C virus in 129 patients with cryptogenic liver disease. Other causes of chronic hepatitis and cirrhosis were ruled out by clinical, serum biochemical and serological techniques. All 129 patients were HBsAg negative, but 28 (22%) had antibody to HBcAg. Sera were tested by radioimmunoassays using recombinant peptides for antibodies to nonstructural (C 100-3 and C33c) and structural regions (C2…

Dot-immunobinding assay with the globular domain of collagen type IV for antiglomerular basement membrane antibodies

A dot-immunobinding assay for the detection of antiglomerular basement membrane antibodies has been developed. The globular domain NC1 of basement membrane collagen type IV was used as antigen. The assay proved to be specific, sensitive, and reproducible. Circulating antibodies in each of 12 sera from patients with florid Goodpasture's syndrome could be demonstrated, whereas sera from patients with Goodpasture's syndrome in clinical remission and various control sera showed no reactivity. The advantages of the dot-blot assay are: the usage of the purified Goodpasature target antigen NCI reduces unspecific binding of IgG; only minimal amounts of antigen are required to give a positive signal…

Immune Reactions in Liver Diseases

Chronic hepatitis is a heterogeneous syndrome with different underlying etiologies. Viruses (hepatitis B virus, non-A, non-B viruses), drugs and even alcohol are regarded as etiological agents. A further subgroup is autoimmune-type chronic hepatitis in which an immunogenetic predisposition is of major importance. Primary biliary cirrhosis has to be separated from these subgroups of chronic hepatitis.

The effect of recombinant alpha-interferon treatment on serum levels of hepatitis B virus-encoded proteins in man.

The effect of alpha-interferon treatment on serum levels of hepatitis B virus-encoded proteins was analyzed in eight patients with chronic type B hepatitis who participated in a pilot study of interferon therapy. Three individuals became HBsAg-negative, 4 lost HBeAg but remained HBsAg-positive and 1 remained positive for both HBsAg and HBeAg. Initiation of interferon treatment was rapidly followed by reduction or loss of hepatitis B virus DNA in the serum but by little immediate change in hepatitis B virus antigen levels. Changes in hepatitis B virus antigens were usually delayed. Loss of HBsAg from the serum was preceded by the sequential disappearance of pre-S-encoded proteins (pre-S1 and…

Methodology and significance of the detection of liver-kidney-microsomal (lkm) autoantibodies in autoimmune-type chronic active hepatitis

Liver-kidney-microsomal (LKM) autoantibodies are diagnostic markers for a subgroup of HBsAg-negative chronic active hepatitis, presumably owing to autoimmunity. They were originally detected by indirect immunofluorescence and can now be evaluated by radioimmunoassay, enzyme-linked immunosorbent assay, and immunoblotting. In immunoblotting LKM-positive sera react strongly with a 50-kilodalton (KD) polypeptide band of microsomes. In immunoelectron microscopy, LKM-positive sera show a binding with membranes of the endoplasmic reticulum. The LKM antigen was further identified on various isoenzymes of cytochrome P-450. Immunofluorescence is still the method of choice for screening sera routinely…

Experimental autoimmune hepatitis: Disease induction, time course and t-cell reactivity

This study describes a murine model of autoimmune hepatitis: experimental autoimmune hepatitis. Experimental autoimmune hepatitis could be induced most effectively in male C57BL/6 mice by intraperitoneal immunization with the 100,000 g supernatant of syngeneic liver homogenate (S-100) in complete Freund's adjuvant. BALB/C and C3H mice were less susceptible than C57BL/6 mice. Experimental autoimmune hepatitis could not be induced in Lewis rats. Intraperitoneal immunization was more effective than intramuscular or subcutaneous injections, and the amount of protein administered above a threshold was of little influence. A single intraperitoneal injection of S-100 in complete Freund's adjuvant …

Hepatitis C virus prevalence and level of intervention required to achieve the WHO targets for elimination in the European Union by 2030: a modelling study

Background Hepatitis C virus (HCV) is a leading cause of liver-related morbidity and mortality worldwide. In the European Union (EU), treatment and cure of HCV with direct-acting antiviral therapies began in 2014. WHO targets are to achieve a 65% reduction in liver-related deaths, a 90% reduction of new viral hepatitis infections, and 90% of patients with viral hepatitis infections being diagnosed by 2030. This study assessed the prevalence of HCV in the EU and the level of intervention required to achieve WHO targets for HCV elimination. Methods We populated country Markov models for the 28 EU countries through a literature search of PubMed and Embase between Jan 1, 2000, and March 31, 201…

Untersuchungen zum Verteilungsmuster von Prä S und S-kodierten viralen Hüllproteinen des Hepatitis B Virus (HBV) auf molekularer Ebene im Serum und Lebergewebe von chronischen HBsAg-Trägern

Die biologische Bedeutung der PraS-kodierten Hepatitis B Virus (HBV) — Hullproteine — insbesondere ihre Regulation innerhalb der Leberzelle — ist noch unklar. Daher war es Ziel unserer Untersuchungen, die PraS- und S-kodierten Hullproteine vergleichend im Serum und im Lebergewebe auf molekularer Ebene zu untersuchen.

Relationship between the target antigen of liver-kidney microsomal (LKM) autoantibodies and rat isoenzymes of cytochrome P-450

Chronic active hepatitis (CAH) is a clinical syndrome of different etiologies. Liver-kidney microsomal (LKM) autoantibodies characterize a subgroup of HBsAg negative CAH, which is considered to be an autoimmune liver disease. By immunoblotting analysis (IB) LKM positive sera have been shown to react strongly with a poly-peptide band at 50 kD. Therefore we investigated various rat microsomal enzymes with a molecular weight around 50 kD as potential candidate target antigens. These included epoxide hydrolase, cytochrome P-450 reductase, and phenobarbital-inducible isoenzymes of cytochrome P-450 (PB1, PB2, PB3a, PB3b). By radioimmunoassay (RIA) and IB LKM positive sera were shown to react with…

Reactivation of chronic type B hepatitis: the effect on expression of serum HBV-DNA and pre-S encoded proteins.

Hepatitis B markers were studied in seven patients with reactivated liver disease. Reactivation of chronic type B hepatitis, as indicated by the reappearance of hepatitis B e antigen (HBeAg) in the serum, was characterised by the appearance of hepatitis B virus-DNA (HBV-DNA) in the serum. The expression of pre-S 1 encoded protein remained unchanged in five of seven patients, and poly-HSA as a marker for pre-S 2 encoded protein remained detectable in six of seven patients before and after reactivation of chronic hepatitis. The level of serum HBV-DNA correlated well with the level of liver enzymes, which rose from normal to various levels after reactivation of the liver disease. The data sugg…

In vitro secretion of specific antimitochondrial antibodies in primary biliary cirrhosis

Antimitochondrial antibodies are present in the serum of virtually all patients with primary biliary cirrhosis. They have a well-defined antigen reactivity that is diagnostic for the disease. The role of these autoantibodies in the disease process remains to be defined. In this study we show that antimitochondrial antibodies can be produced in vitro by peripheral blood lymphocytes, that the cells producing antimitochondrial antibodies are present in the peripheral blood in a high frequency and seem to be maximally activated. Stimulation with pokeweed mitogen did not augment the in vitro production of antimitochondrial antibodies in patients nor did it induce the production of these antibodi…

Autoantibodies in experimental autoimmune hepatitis

Experimental autoimmune hepatitis (EAH) can be induced in mice by immunization with syngeneic soluble liver antigens in complete Freund's adjuvant. It has previously been shown that autoreactive T cells play an important role in this animal model of autoimmune hepatitis. We have studied the occurrence of liver autoantibodies in EAH. Characteristic autoantibodies appeared several weeks after disease induction and antibody titres continued to rise when histological and biochemical signs of disease activity had already regressed. Autoantibodies in EAH seemed to recognize autoantigens other than those present in autoimmune chronic active hepatitis patients. We conclude that autoantibodies arise…

Regulation of cytochrome P450 IID by acute phase mediators in C3H/HeJ mice.

Abstract Cytochrome P450 IID6 is a drug metabolizing enzyme and the major target antigen in LKM-1 antibody positive chronic active hepatitis. The histological hallmark of chronic active hepatitis is a lymphocytic infiltrate in the liver. It is unknown whether and how cytokines produced and secreted by these tissue infiltrating mononuclear cells regulate the cellular expression of cytochrome P450 IID6. To study the effect of interleukin 1, tumor necrosis factor and interleukin 6 on the hepatocellular RNA expression of cytochrome P450 IID, we injected each of the cytokines in C3H HeJ mice. We found a time-dependent suppression of the cytochrome in the liver. Six hours after the intraperitonea…

Antiglomerular basement membrane antibodies in human sera: Detection by a modified micro-ELISA

An enzyme-linked immunosorbent assay (ELISA) for detection of antibodies to human glomerular basement membrane has been developed. Special emphasis has been put on the choice of microtiter plates which were coated with a collagenase digest of human glomerular basement membrane. Results differed markedly between the different microtiter plates. Best results were obtained with a flexible polyvinylchloride microtiter plate with flat wells (Dynatec). This plate exhibited the highest positive/negative ratio and the lowest intraassay standard deviation. Optimal conditions for each step in the ELISA have been determined. The assay proved to be specific, sensitive, and reproducible. Circulating ant…

Autoantibodies to human asialoglycoprotein receptor in autoimmune-type chronic hepatitis.

Autoantibodies to the human asialoglycoprotein receptor (anti-h-ASGPR) were studied with a solid-phase ELISA in the sera of 421 patients with inflammatory liver diseases, 288 patients with various other disorders and 31 controls. Anti-h-ASGPR were found predominantly in autoimmune chronic active hepatitis (44 of 88, 50%) and were closely related to inflammatory activity. In a subpopulation of these patients with untreated, biopsy-proven active disease or relapse, 15 of 17 were positive (88%). In contrast, only 11 of 204 patients (5.3%) with viral hepatitis were anti-h-ASGPR receptors-positive (chi 2 analysis; p less than 0.001). We also compared the occurrence of anti-h-ASGPR with antibodie…

Relationship of pre-S encoded antigens in liver and clinical manifestations of chronic hepatitis B infection.

Pre-S1 and pre-S2 encoded antigens of hepatitis B virus were localized in liver tissue using monoclonal antibodies. They were found to be exclusively expressed in the cytoplasm of liver cells. Cell bound pre-S1 encoded protein was often detected in patients with chronic liver disease and viremia. Only a small number of the HBsAg positive cells also contained pre-S1 antigen. There was no correlation with nuclear HBcAg. Livers of non-viremic HBsAg carriers contained many HBsAg expressing liver cells, that were frequently also positive for pre-S2 encoded protein but contained no detectable pre-S1 encoded protein at all. It remains open whether cell bound pre-S2 containing proteins of middle si…

Significant autoimmune markers of autoimmune liver disorders: Current status

Strain differences in experimental autoimmune hepatitis

The human hepatic asialoglycoprotein receptor is a target antigen for liver-infiltrating T cells in autoimmune chronic active hepatitis and primary biliary cirrhosis.

Autoantibodies to the human hepatic asialoglycoprotein receptor have been found in nearly 50% of the sera of patients with autoimmune chronic active hepatitis and in 15% of patients with primary biliary cirrhosis. In this study we demonstrate that the human hepatic asialoglycoprotein receptor is also a target antigen for T cell-mediated immune responses. Peripheral blood lymphocytes of 37% (7 of 19) of patients with autoimmune chronic active hepatitis and 33% (2 of 6) of patients with primary biliary cirrhosis showed a proliferative response to highly purified human hepatic asialoglycoprotein receptor, whereas no proliferation was found with peripheral blood lymphocytes of patients with chr…

Correlation of anti-cytoskeleton antibody activities in synovial fluid with interleukin-6 in patients with osteoarthritis and inflammatory joint disease

Synovial fluids and sera from patients with rheumatoid arthritis, psoriatic arthritis, yersinia arthritis, Behçet's syndrome, Crohn's disease, and osteoarthritis were tested for antinuclear antibodies and antibodies to five cytoskeletal components in sensitive enzyme-linked immunosorbent assay (ELISA) systems and for IL-6 concentrations in a proliferation assay (IL-6 dependent hybridoma cell line B13.29, subclone B9). Statistically significant correlations between antibody activities and IL-6 levels were found for vimentin antibodies (r = 0.56; p less than 0.05) and actin antibodies (r = 0.44; p less than 0.05). In patients with chronic and active disease like rheumatoid arthritis and psori…