Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q16637 (SMA)
 8,107 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic inflammatory liver diseases can be induced by virus infections, toxic-metabolic factors and/or autoimmune mechanisms. This overview deals with the immunopathogenesis of chronic hepatitis B and C and autoimmune hepatitis (AIH). 1. Chronic hepatitis B: The immune response to HBV-antigens is responsible both for viral clearance and disease pathogenesis during HBV-infection. The humoral immune response to HBsAg contributes to the clearance of circulating virus particles, the cell mediated immune response to HBsAg, HBcAg and polymerase antigen eliminates infected cells. The class I- and class II restricted T-cell-responses to HBV is strong, polyclonal and multispecific in acute HB with successful clearance of the virus, but weak or incomplete in chronic HB with viral persistence. In addition to ineffective immune response host and viral factors as well as abnormalities in virus-host interactions may be the main reasons for the maintenance of HBV-carrier status. 2. Chronic hepatitis C develop in more than 60% of infected patients. There is increasing evidence that the immune response to HCV-epitopes plays an important role in the course and the pathogenesis of the disease. It has been shown that CD4+ and CD8+ T-cells recognize viral peptides in the presence of class I and II molecules. The fine specificity and functional significance of liver infiltrating and peripheral blood T-cells demonstrate HCV specific immunodominant epitopes targeted by class Ii restricted CD4+ cells in patients with chronic HCV infection. The T-cell response correlates with disease activity. The cytokine release of T-cells resemble a TH1-like profile. Studies of the humoral immune response to HCV show a correlation between IgM-anti-HCV and disease activity. In vitro and in vivo anti-HCV secretion by PBMC is due to persistent antigenic stimulation of B-cells by ongoing production of viral antigens and reflects HCV replication in PBMC. Of special interest are several immune mediated disease and immune abnormalities in chronic hepatitis C. 3. Autoimmune hepatitis (AIH) is a distinct group of acute and chronic necro-inflammatory disorders of unknown etiology characterized by immunological and autoimmunological features including the presence of autoantibodies but without an antecedent of viral infections. Marker autoantibodies define 3 subtypes: Type I (ANA/SMA), Type II (LKM1-AB), Type II (SLA-AB). AIH is associated with a distinct genetic background (HLA A1, B8, DR3 or DR4). Several studies clearly demonstrate that liver cell damage in AIH is mediated by autoimmune reactions against normal constituents of hepatocytes. Although the precise mechanisms are not yet fully understood, there is now considerable evidence that autoantigens of the hepatocellular membrane in particular the ASGPR are important targets of liver damaging autoreactions in AIH. Cellular and humoral immune reactions against the human ASGPR correlate with disease activity and usually disappear under immunosuppressive therapy.
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PMID:[Immunopathology of chronic liver diseases]. 860 Jun 84

The number of autoantibodies associated with chronic liver disease continues to burgeon and characterization of these immunoreactivities will undoubtedly enhance understanding of the autoantigens that are targeted by cytodestructive immunocytes. Assays for the majority of these immunoserological species are not generally available and in most instances, assessments are restricted to individual laboratories with vested interests in characterizing a particular species. For clinical diagnosis and management of autoimmune liver disease, assays for ANA, SMA, anti-LKM1 and AMA are essential. This conventional armamentarium, however, must be upgraded on a regular basis to ensure availability and application of the most useful assays. Unfortunately, there are no formal mechanisms for improving the diagnostic resources and standardizing testing strategies. An important first step must be taken by the basic laboratories that advocate individual assay systems. These facilities must share methodologies and exchange serum samples so that the most clinically pertinent and cost-effective immunoserological batteries can be defined and promulgated. Industry can then respond to need and facilitate the commercialization of assays for general use. Currently, the assays that warrant dissemination are those that detect antibodies to the E2 subunits of the pyruvate dehydrogenase complex and antibodies to asialoglycoprotein receptor. Both assays have high diagnostic specificity and each reflects reactivity to an important target autoantigen of probable pathogenic importance. Each autoantibody species can supplant conventional assays such as those for AMA and ANA and they each may impart useful clinical information. In the case of antibodies to the E2 subunits, titres may reflect histological progression of PBC. In the case of anti-ASGPR, disappearance of the autoantibodies in patients with autoimmune hepatitis may secure a confident treatment end-point. Great progress has been made in defining the immunoserological manifestations of chronic liver disease but little has been done to distribute the resources.
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PMID:Autoantibodies. 890 2

The aim of this study was to determine the incidence of autoantibodies to asialoglycoprotein receptor (ASGPR, anti-ASGPR) in chronic hepatitis C patients and to characterize the anti-ASGPR-positive and anti-ASGPR-negative patients in more detail. A total of 79 chronic hepatitis C patients were screened for the presence anti-ASGPR by ELISA. Anti-ASGPR were detected in 11 (13.9%) patients. No significant differences were found between the anti-ASGPR-positive and anti-ASGPR-negative patients in age, alanine transaminase (ALT) activity, histological findings and response and tolerance to alpha-interferon (alpha-IFN) therapy. The male predominance in the anti-ASGPR positive group was statistically significant. It was surprising that other tested autoantibodies (antinuclear autoantibodies [ANA], smooth muscle autoantibodies [SMA], type 1 liver-kidney microsome autoantibodies [LKM-1], anti-thyroglobulin and thyroid microsome autoantibodies) and increased levels of immunoglobulins A, G and/or M were observed significantly more frequently in the anti-ASGPR-negative group.
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PMID:Autoantibodies to asialoglycoprotein receptor in chronic hepatitis C patients. 1139 82

No longitudinal study has investigated whether autoantibody titres and serum IgG levels correlate with disease activity in autoimmune liver disease. To determine this, we investigated prospectively 19 patients on 254 occasions between 10 months to 5 years from diagnosis. Nine had anti-nuclear and/or anti-smooth muscle antibody (ANA/SMA) positive autoimmune hepatitis (type 1 AIH), 5 liver kidney microsomal type 1 (LKM-1) positive AIH (type 2 AIH) and 5 ANA/SMA positive autoimmune sclerosing cholangitis (ASC). Correlation between IgG levels, titres of ANA, SMA and LKM-1 and levels of the organ specific autoantibodies anti-liver specific protein (anti-LSP), and anti-asialoglycoprotein receptor (anti-ASGPR) with biochemical evidence of disease activity, as measured by serum aspartate amino transferase (AST) levels, was sought during the course of the disease. AST levels correlated with levels of anti-LSP, anti-ASGPR and IgG in type 1 and 2 AIH, but not in ASC. Positive correlation with AST was also observed for LKM-1 titres in type 2 AIH and for SMA titres in type 1 AIH, but not in ASC. In both AIH and ASC, AST levels correlated with the T cell-dependent immune responses anti rubella IgG and anti tetanus toxoid IgG, but not with the T cell-independent IgG2 response to pneumococcal capsular polysaccaride. Our results indicate that measurement of organ and non-organ specific autoantibodies and IgG levels may be used to monitor disease activity in AIH.
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PMID:Organ and non-organ specific autoantibody titres and IgG levels as markers of disease activity: a longitudinal study in childhood autoimmune liver disease. 1276 77

Autoimmune hepatitis (AIH) is a disease of unknown etiology, characterized by liver-related autoantibodies. Autoimmune hepatitis is subdivided into two major types: AIH type 1 is characterized by the detection of ANA, SMA, ANCA, anti-ASGP-R, and anti-SLA/LP. Autoimmune hepatitis type 2 is characterized to be mainly related with drug-metabolizing enzymes as autoantigens, such as anti-LKM (liver-kidney microsomal antigen)-1 against CYP2D6, anti-LKM-2 against CYP2C9-tienilic acid, anti-LKM-3 against UGT1A, and anti-LC1 (liver cytosol antigen)-1 and anti-APS (autoimmune polyglandular syndrome type-1) against CYP1A2, CYP2A6, and others. Anti-LKM-1 sera inhibited CYP2D6 activity in vitro but did not inhibit cellular drug metabolism in vivo. CYP2D6 is the major target autoantigen of LKM-1 and expressed on plasma membrane (PM) of hepatocytes, suggesting a pathogenic role for anti-LKM-1 in liver injury as a trigger. Anti-CYP1A2 was observed in dihydralazine-induced hepatitis, and radiolabeled CYP1A2 disappeared from the PM with a half-life of less than 30 min, whereas microsomal CYP1A2 was stably radiolabeled for several hours. Main antigenic epitopes on CYP2D6 are aa 193-212, aa 257-269, and aa 321-351; and D263 is essential. The third epitope is located on the surface of the protein CYP2D6 and displays a hydrophobic patch that is situated between an aromatic residue (W316) and histidine (H326). Some drugs such as anticonvulsants (phenobarbital, phenytoin, and carbamazepine) and halothane are suggested to induce hepatitis with anti-CYP3A and anti-CYP2E1, respectively. Autoantibodies against CYP11A1, CYP17, and/or CYP21 involved in the synthesis of steroid hormones are also detected in patients with adrenal failure, gonadal failure, and/or Addison disease.
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PMID:Autoantibodies against CYP2D6 and other drug-metabolizing enzymes in autoimmune hepatitis type 2. 1574 2