Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders

McFarlane, Barbara M.; McSorley, C.; Vergani, Diego; McFarlane, I G; Williams, Roger

doi:10.1016/s0168-8278(86)80026-5

Cited by 139 publications

(48 citation statements)

References 35 publications

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“…Several arguments suggest an involvement of ASGP-R in immune responses. First, ASGP-R has been previously suggested as being one potential target in chronic hepatic autoimmune disease in humans (40) and, experimentally, antibodies against ASGP-R are produced in animals challenged with woodchuck hepatitis virus (15). Second, HCV is known to favor the occurrence of autoantibodies, such as those observed in autoimmune thyroid diseases (55).…”

Section: Discussionmentioning

confidence: 99%

Role of the Asialoglycoprotein Receptor in Binding and Entry of Hepatitis C Virus Structural Proteins in Cultured Human Hepatocytes

Saunier

Triyatni

Ulianich

et al. 2003

J Virol

118

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We used a baculovirus-based system to prepare structural proteins of hepatitis C virus (HCV) genotype 1a. Binding of this preparation to cultured human hepatic cells was both dose dependent and saturable. This binding was decreased by calcium depletion and was partially prevented by ligands of the asialoglycoprotein receptor (ASGP-R), thyroglobulin, asialothyroglobulin, and antibody against a peptide in the carbohydrate recognition domain of ASGP-R but not preimmune antibody. Uptake by hepatocytes was observed with both radiolabeled and dye-labeled HCV structural proteins. With hepatocytes expressing the hH1 subunit of the ASGP-R fused to green fluorescent protein, we could show by confocal microscopy that dye stain cointernalized with the fusion protein in an area surrounding the nucleus. Internalization was more efficient with a preparation containing p7 than with one that did not. The two preparations bound to transfected 3T3-L1 cells expressing either both (hH1 and hH2) subunits of the ASGP-R (3T3-22Z cells) or both hH1 and a functionally defective variant of hH2 (3T3-24X cells) but not to parental cells. Additionally, uptake of dye-labeled preparation containing p7 was observed with 3T3-22Z cells but not with 3T3-L1 or 3T3-24X cells or with the preparation lacking p7, suggesting that p7 regulates the internalization properties of HCV structural proteins. Our observations suggest that HCV structural proteins bind to and cointernalize with the ASGP-R in cultured human hepatocytes.Hepatitis C virus (HCV) infection has become a major health problem affecting an estimated 170 million people worldwide. Persistent infection occurs in more than 70% of people infected with HCV, which may be complicated by cirrhosis and/or hepatocellular carcinoma (24, 33). Despite highly competitive and extensive research in this field, a highly effective treatment is not yet available. The mainstay of anti-HCV therapy, alpha interferon (IFN-␣) or pegylated IFN-␣, together with ribavirin leads, at best, to viral clearance in ca. 41 to 54% of patients infected with HCV genotype 1a (34,38). Since mechanisms of HCV infection remain unclear, characterization of these mechanisms is now a major issue for the development of new strategies for anti-HCV treatment and prevention.

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Section: Discussionmentioning

confidence: 99%

Role of the Asialoglycoprotein Receptor in Binding and Entry of Hepatitis C Virus Structural Proteins in Cultured Human Hepatocytes

Saunier

Triyatni

Ulianich

et al. 2003

J Virol

118

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“…These numbers contrast the results of a previous report, where lower percentages of anti-ASGPR in patients with ALD have been reported. 16,28 However, in this study, mainly patients with ALD without cirrhosis were evaluated.…”

Section: Discussionmentioning

confidence: 99%

Asialoglycoprotein receptor facilitates hemolysis in patients with alcoholic liver cirrhosis

et al. 2004

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Hemolysis in patients with advanced alcoholic liver disease is a common clinical problem and indicates an unfavorable prognosis. In many cases, the etiology of the hemolysis remains unknown. We observed three patients with alcoholic liver disease, suffering from severe hemolytic anemia, requiring multiple blood transfusions. Steroid therapy was ineffective and two of the patients died. All patients had a soluble variant of the human asialoglycoprotein receptor (s-ASGP-R) in their serum, as well as high titers of autoantibodies against this receptor (anti-ASGP-R). Consecutively, examination of 60 patients with alcoholic liver disease revealed a high incidence for s-ASGP-R (36%) and anti-ASGP-R (27%) in patients with alcoholic liver cirrhosis (ALC) compared to patients with cirrhosis due to viral hepatitis. The potential etiology of hemolysis was studied in vitro on erythrocytes from patients with ALC and from healthy donors. Isolated ASGP-R but not anti-ASGP-R bound to the surface of erythrocytes preferentially of blood group A1 and caused dose-dependent agglutination and hemolysis, while this phenomenon was much lower using erythrocytes of the blood group B and almost absent with blood group O-erythrocytes. Furthermore, agglutination and hemolysis only occurred in erythrocytes from ALC-patients or after the pretreatment of cells with neuraminidase. ASGP-R induced agglutination and hemolysis was blocked by the competitive ASGP-R inhibitor asialofetuin. In conclusion, our results indicate a new, non-immunological mechanism for hemolysis in patients with alcoholic liver disease, mediated through agglutination by a soluble variant of the human asialoglycoprotein receptor and mechanical shear stress.

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“…Neurological symptoms in patients with HBV-related hepatitis can be ascribed not only to the side effects of drugs used for treatment, including interferon ( 1 0), but also to HBVitself, as exemplified by polyneuropathy due to the deposition of immunecomplexes (ll, 12). According to McFarlane et al, antibodies against hepatic asialoglycoprotein receptor, which have molecular analogy with AchR, can be detected in sera of patients with either autoimmuneor HBV-relatedchronic active hepatitis (13). However,whether these antibodies can react with AchRpathogenetically remains unclear.…”

Section: Discussionmentioning

confidence: 99%

Myasthenia Gravis with Membranous Nephropathy, Successfully Treated with Extended Total Thymectomy.

et al. 2000

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A 46-year-old womanshowed proteinuria and hematuria after left blepharoptosis, and revealed a histopathology of membranousnephropathy (MN) at renal biopsy. She was diagnosed as having myasthenia gravis (MG)because of a positive edrophoniumtest and anti-acetylcholine receptor (AchR) antibodies in serum. Wefound a decrease in antiAchRantibodies after extended total thymectomy, in parallel with an improvement in both urinary findings and myasthenic symptoms. In this case, MGpreceded MNand the thymectomy was effective for both diseases, suggesting that the thymus might play an important role in the pathogenesis of MN. (Internal Medicine 39: 490-494, 2000)

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Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders

Cited by 139 publications

References 35 publications

Role of the Asialoglycoprotein Receptor in Binding and Entry of Hepatitis C Virus Structural Proteins in Cultured Human Hepatocytes

Role of the Asialoglycoprotein Receptor in Binding and Entry of Hepatitis C Virus Structural Proteins in Cultured Human Hepatocytes

Asialoglycoprotein receptor facilitates hemolysis in patients with alcoholic liver cirrhosis

Myasthenia Gravis with Membranous Nephropathy, Successfully Treated with Extended Total Thymectomy.

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