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)

Twenty patients found LKM antibody positive during the routine screening for autoantibodies, were studied for the association with other autoantibodies. Sixteen sera (80%) were found positive either for ANA (50%) or SMA (50%) or both (20%). Eleven patients (55%) were over 40 years old, 3 patients were HBsAg+ve, 4 have toxic and alcohol-related liver disease. These results provide evidence that the LKM antibody is not confined to young people chronic active hepatitis, but is present also in CALD of adult with various etiology. Its association with other autoantibodies (especially ANA) suggest that also LKM could be a marker of autoimmunity. The presence of ANA may be an expression of more severe stages of the disease.
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PMID:[The microsomal antibody (LKM) in liver pathology: its association with other autoantibodies]. 697 May 82

To clarify the importance of ethnic and geographic factors in chronic active hepatitis (CAH), HBV markers and autoantibodies (AMA, ANA, SMA), have been compared in 158 patients with biopsy-proven CAH from New York City and in 92 patients with CAH from Milan. HBsAg-positive CAH was more frequently observed in Milan (49%) than in New York City (27%). However, among HBsAg-positive patients, HBcAg, HBeAg, and epidemiologic risk factors for acquisition of HBV infection were more frequently found in New York than in Italy. The prevalence of HBsAg-negative, anti-HBc-positive CAH and cryptogenic CAH was similar in the two cities, while autoimmune CAH was more frequently observed in New York (20%) than in Milan (2%). In particular, the prevalence of autoimmune hepatitis was higher among Jewish patients than among patients of Anglo-Saxon or Latin ethnic background in New York. Thus, environmental and/or ethnic factors may influence the prevalence of the four major types of CAH.
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PMID:Geographic differences in HBV related, autoimmune, and cryptogenic chronic active hepatitis. 717 41

In summary, type 1 autoimmune hepatitis is infrequently associated with serologic markers of viral infection, and there is no direct evidence that viruses are important causes of this disease. Patients seropositive for anti-LKM1 are commonly infected with HCV, but these patients have predominant features of chronic viral hepatitis and frequently lack antibodies to P450IID6. Such patients respond to therapy with interferon and should be distinguished from patients with type 2 autoimmune hepatitis who have anti-P450IID6, seronegativity for anti-HCV, and responsiveness to corticosteroids. In patients with ANA and/or SMA seropositivity and anti-HCV, a false-positive reaction for anti-HCV must be excluded by recombinant immunoblot assay. Patients with false anti-HCV seropositivity should be treated with corticosteroids. In contrast, patients with a true viral infection and low-titer autoantibodies should be treated with interferon. In patients with true viral infection and high titers of auto-antibodies, the treatment decision must balance the autoimmune and viral manifestations. An empiric trial of corticosteroids is justified if autoimmune features predominate.
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PMID:Autoimmune hepatitis and viral infection. 752 73

Viral infections are considered a possible trigger of autoimmune diseases. In autoimmune liver diseases the hepatotropic viruses, especially hepatitis C virus (HCV), have received particular attention as possible etiological agents. The present study was undertaken to investigate the relation between hepatitis virus infections and autoimmune liver diseases. We found a very low incidence of HCV infection in patients with autoimmune liver diseases. Only 5% (n = 7) of patients with AIH types I and III had antibodies against HCV antigens, but only two of these seven were HCV-RNA positive. Similar results were obtained in patients with PBC and PSC. Furthermore, the coexistence of LKM autoantibodies with chronic HC is a rare event and less common than low-titer ANA and SMA in viral liver diseases. In conclusion, a link between hepatitis viruses B or C and AI-liver diseases is very unlikely. Autoantibodies in viral liver diseases appear to be an expression of a generalized immune activation by cytokines, as observed during interferon treatment in viral liver diseases.
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PMID:The role of autoimmunity in hepatitis C infection. 760 86

We prospectively measured serum alkaline phosphatase (ALP), aspartate and alanine transaminase (AST/ALT), and tested sera for antinuclear, smooth-muscle, and antimitochondrial antibodies (ANA, SMA, AMA) in our patients with celiac sprue to determine the prevalence of associated liver abnormalities and its relevance to clinical management. Of 129 patients, ALP was the only elevated enzyme in 12 (9%) and in most cases was not thought to reflect significant liver disease. Seventeen (13%) had elevated AST and/or ALT with normal ALP. Levels normalized in 15 patients after dietary gluten exclusion and remained elevated in 2 noncompliers. Two patients (2%) with elevated AST, ALT, and ALP underwent further investigation: one had negative autoantibodies, liver biopsy, and endoscopic retrograde cholangiography and the other had ANA-positive chronic active hepatitis; enzymes in both cases improved with a gluten-free diet. There was no significant association between elevated AST/ALT and positive ANA/SMA; no patient had AMA. Abnormalities in liver enzymes are common in celiac sprue, but usually respond to dietary gluten exclusion. We propose that there is no need for invasive liver investigation in these patients unless there is more specific evidence of primary liver disease or failure of dietary response.
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PMID:Liver abnormalities associated with celiac sprue. How common are they, what is their significance, and what do we do about them? 766 16

An etiopathological link between hepatitis virus infection and autoimmune liver disease, in particular autoimmune hepatitis has been suggested. In some patients features of both viral and autoimmune disease are present. We have studied 352 patients with autoimmune liver disease and 507 patients with viral hepatitis for diagnostic characteristics as well as for evidence of an etiological connection. 38 of the 201 patients with hepatitis C (19%) and 42 of the 306 patients with hepatitis B (14%) had significant titres of autoantibodies (ANA, SMA or LKM). SLA autoantibodies were found exclusively in patients with autoimmune liver disease. LKM auto-antibody was found in only one of the 201 HCV patients. Evidence of past or present hepatitis B virus and past hepatitis A virus infection was most common in the hepatitis C virus patients and least common in autoimmune hepatitis. 28 of the 352 patients with autoimmune liver diseases tested positive in the second generation anti-HCV ELISA, but only five patients (two with autoimmune hepatitis, one with primary sclerosing cholangitis and two with primary biliary cirrhosis) were positive in confirmatory anti-HCV assays, and only in these could HCV-RNA be isolated. Autoimmune hepatitis patients had significantly higher transaminase, GLDH and IgG levels. HLA-B8, HLA-DR3 and HLA-DR4 were significantly more common in autoimmune hepatitis. Distinction between autoimmune liver disease and viral hepatitis C could be made reliably on clinical and laboratory grounds. Our data show that a link between hepatitis A, B, or C virus infection and autoimmune liver diseases is highly unlikely.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relation between autoimmune liver diseases and viral hepatitis: clinical and serological characteristics in 859 patients. 852 56

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

We present 10 Italian patients with type 2b autoimmune hepatitis (anti-LKMI positivity) and HCV infection. 6 patients had IgG concentrations above the upper limit of normal and all had histological features of chronic autoimmune hepatitis or chronic persistent hepatitis or cirrhosis. ANA and SMA were positive in 2 patients, pANCA in 3 patients. Anti-GOR were negative in all patients, 6 of them were HLA B8 DR3 and 2 HLA B8 DR4. Antibodies to HCV (tested by ELISA 2nd and 3rd generation) were positive in all patients and in 9 subjects were detected HCV RNA. The two patients with positivity for ANA and SMA were treated successfully with corticosteroids, but they relapsed after the drug withdrawal; the others received interferon, that had to be suspended in 2 patients because inducing an autoimmune thyroiditis. Although, at present, it is still not known if HCV is a really trigger factor in developing autoimmunity or if the two diseases are coincidental, the authors suggest that it is important for clinicians to use appropriate treatment strategies on the basis of the predominant illness.
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PMID:Type 2 autoimmune hepatitis and hepatitis C viraemia. 876 75

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

Interferon (IFN) has become the standard therapy for chronic hepatitis C. The use of IFN should be accompanied by adequate diagnosis and management using standard practices as well as new and sophisticated techniques now available. A liver biopsy performed prior to IFN therapy initiation remains the standard for adequate histological diagnosis of HCV disease as well as determination of disease severity and the presence of liver cirrhosis. ALT normalization is not adequate to determine complete short-term response to IFN treatment. Adverse effects resulting from IFN therapy include a flulike syndrome, hematologic effects, neuropsychiatric effects, and thyroid abnormalities. The majority of these can be adequately managed without discontinuation of IFN treatment. However, preexisting psychiatric conditions are a contraindication to IFN therapy. IFN treatment also is contraindicated in patients with autoimmune hepatitis (AIH). Therefore, it is important to distinguish AIH from chronic HCV infection using HCV-RNA analysis and determination of autoimmune titers (including anti-LKM antibodies, anti-SMA, and ANA). Recently reported adverse effects of IFN include respiratory and ocular effects. Serological diagnosis of HCV infection has evolved to the use of second- and third-generation ELISA tests. Although sophisticated, these tests cannot distinguish between active and quiescent infection, and therefore are of limited value in monitoring treatment response. Several other techniques have been suggested: the ratio between IgG and IgM class anti-HCV core antibodies, detection of antibodies against a glycosylated recombinant product of the E2 envelope glycoprotein, and several different polymerase chain reaction (PCR) techniques. The latter appears to be the most promising. Use of these techniques should be incorporated into the monitoring of IFN therapy to assist in the evaluation of adequate treatment response, the need for treatment alteration, and estimation of relapse risk upon treatment cessation.
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PMID:Managing patients on interferon therapy. 901 69


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