Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019163 (hepatitis B)
 38,309 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence is presented to suggest that an auto-immune response to a liver-specific lipoprotein antigen on the surface of hepatocytes is responsible for the progressive liver damage in active chronic hepatitis, and that in many cases infection with the hepatitis B virus is important in the initiation of the disease process. B cells appear to play a major role in the auto-immune response and may be activated by T cells reacting with viral antigens on the surface of infected hepatocytes. A postulated defect in humoral antibody production in HBAg-positive cases allows continued reinfection of the liver by the hepatitis B virus, persistence of a virus-directed T cell response and constant activation of B cells reacting with the liver-specific lipoprotein. In the HBAg -negative group the disease is also, in many cases initiated by an acute hepatitis, but here the auto-immune response continues after elimination of the virus because of a defect in the suppressor function of T cells which fail to turn off the autoreactive B cells. The histocompatibility antigen, HL-A8, may be a marker for such a defect in suppressor T cells - its increased frequency in active chronic hepatitis is restricted to the HBAg-negative cases. Finally, the hypothesis suggests how specific immunotherapy, either antibody to HBAg or Transfer Factor, could be given to correct the basic defects which lead to persistence of the auto-immune process.
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PMID:Immunopathology of hepatitis B antigen positive and negative active chronic hepatitis. 108 61

In order to evaluate the role of histocompatibility antigen (HLA) class 1 antigens in the pathogenesis of liver cell necrosis, HLA class 1 antigens on hepatocytes were studied in the liver biopsy materials from 20 patients with chronic hepatitis B by the peroxidase-labeled antibody method using a monoclonal antibody to human HLA-A, B, C (Cappel Laboratories). Both increased expression of HLA class 1 antigens on the hepatocytes and decreased distribution of intrahepatic hepatitis B core antigen (HBcAg) were observed in patients with an exacerbation of the inflammatory activity. These findings suggest that expression of HLA class 1 antigens on the hepatocytes may be increased when an exacerbation of inflammatory activity develops, and may be compatible with the concept that expression of these antigens plays and important role for the lysis of hepatitis B virus (HBV)-infected liver cells by cytotoxic T cells. Furthermore, in seven patients, expression of HLA class 1 antigens was studied in the liver before and after treatment with human lymphoblast interferon (IFN)-alpha, recombinant IFN-alpha or IFN-beta. Increased expression of HLA class 1 antigens was observed in patients with decreased intrahepatic HBcAg and DNA-P in sera after IFN treatment. These results also suggest that the increase of HLA class 1 antigens by IFN may be related to the immune mechanism for the effective elimination of HBV.
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PMID:Immunohistochemical study of HLA class 1 antigens on the hepatocytes of patients with chronic hepatitis B. 242 87

A method is presented for locating protein antigenic determinants by analyzing amino acid sequences in order to find the point of greatest local hydrophilicity. This is accomplished by assigning each amino acid a numerical value (hydrophilicity value) and then repetitively averaging these values along the peptide chain. The point of highest local average hydrophilicity is invariably located in, or immediately adjacent to, an antigenic determinant. It was found that the prediction success rate depended on averaging group length, with hexapeptide averages yielding optimal results. The method was developed using 12 proteins for which extensive immunochemical analysis has been carried out and subsequently was used to predict antigenic determinants for the following proteins: hepatitis B surface antigen, influenza hemagglutinins, fowl plague virus hemagglutinin, human histocompatibility antigen HLA-B7, human interferons, Escherichia coli and cholera enterotoxins, ragweed allergens Ra3 and Ra5, and streptococcal M protein. The hepatitis B surface antigen sequence was synthesized by chemical means and was shown to have antigenic activity by radioimmunoassay.
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PMID:Prediction of protein antigenic determinants from amino acid sequences. 616 91

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.
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PMID:[Development of chronic active hepatitis of the autoimmune type following hepatitis B virus infection with HBSAg-persistence. 4 case reports]. 671 67

With a monoclonal antibody which reacts with all HLA class 1 antigens it was found that these antigens are not uniformly distributed in all nucleated cells. Rather HLA class 1 antigens are restricted in their distribution to lymphoid cells, endothelial cells of small vessels, and certain epithelia including mammary duct cells. These antigens were not detected on hepatocytes, specialised cells of the central nervous system, or on the tumour cells of 8 out of 17 human mammary cancers. Given the hypothesis that T cells only respond to foreign antigens on cells which share a common major histocompatibility antigen, these results imply that the T cell responses to viral infections of hepatocytes--for example, hepatitis B virus and the CNS--for example, subacute sclerosing encephalitis, are mediated through an antigen system other than HLA class 1. The absence of HLA class 1 antigen on many mammary cancer cells may be of prognostic significance if T cell modulation of tumour growth is mediated through this class of antigens.
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PMID:Distribution of HLA class 1 antigens in normal human tissue and in mammary cancer. 702 3

Persistent hepatitis B virus (HBV) infection often leads to the development of chronic hepatitis, cirrhosis and hepatocellular carcinoma. There is a need to develop new antiviral approaches for the treatment of this disease. We have explored various nucleic acid-based strategies designed to inhibit HBV replication including: the use of antisense RNA and DNA constructs, DNA-based immunization techniques to stimulate broad-based cellular immune responses with particular emphasis on the generation of cytotoxic lymphocyte (CTL) activity to viral structural proteins, hammerhead ribozymes to cleave HBV pregenomic RNA in vitro and dominant negative HBV core mutant proteins as inhibitors of nucleocapsid formation within cells. In order to optimize these antiviral effects, various novel expression vectors have been developed to deliver such DNA constructs to cells. For example, adenoviral vectors carrying genes that encode for dominant negative proteins have been employed to transfect hepatocytes in vitro and in vivo. In addition, plasmid vectors have been produced to promote expression of HBV structural genes following injection into muscle cells as a means to stimulate the host's cellular and humoral immune response in the context of histocompatibility antigen (HLA) class I and II antigen presentation. These experimental approaches may have important implications for the generation of efficient antiviral effects during chronic HBV infection.
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PMID:Nucleic acid-based antiviral and gene therapy of chronic hepatitis B infection. 940 58