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)

To determine the clinical, biochemical, and histological features, and outcome of childhood autoimmune hepatitis (AIH), we reviewed the medical records of 52 children with AIH, 32 (median age: 10 [2-15] years) anti-nuclear and/or smooth muscle antibody (ANA/SMA) positive, 20 (7 [0.8-14] years) liver/kidney microsomal antibody (LKM-1) positive, with median follow-up of 5 years (range 0.3-19). At presentation: 56% had symptoms of prolonged acute hepatitis; LKM-1 positive were younger (P = .011), with higher bilirubin (P = .007), and AST (P = .047); ANA/SMA positive had lower albumin (P = .023); 69% ANA/SMA positive, and 38% LKM-1 positive were cirrhotic (P = .080). ANA/SMA positive had increased frequency of HLA haplotype A1/B8/DR3/DR52a compared with controls (53% vs. 14%, P < .001). Of six (5 LKM-1 positive) with fulminant hepatitis, four were transplanted, one died, and one ANA/SMA positive improved with immunosuppression. Of 47 treated with immunosuppression, 2 (1 LKM-1 positive) died with no remission and 4 (2 LKM-1 positive) were transplanted 8 to 14 years after diagnosis. Immunosuppression was stopped successfully in 19% of ANA/SMA positive after a median of 3 years of treatment, but in none of LKM-1 positive. Baseline bilirubin and international normalized prothrombin ratio (INR) were independent variables predictive of outcome. In conclusion, ANA/SMA positive and LKM-1 positive AIH in childhood have clinical, biochemical, and histological differences, but similar severity and long-term outcome.
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PMID:Autoimmune hepatitis in childhood: a 20-year experience. 904 95

In a pilot study we investigated the effect of ursodeoxycholic acid therapy in 11 patients (mean age 45.8 +/- 13.2 years) with chronic active, ANA- and/or SMA-positive autoimmune hepatitis of moderate severity. All patients were clinical asymptomatic and no indication for immunosuppressive therapy could be established in any patient. After a washout period of at least 3 months, the treatment was administrated with 500 mg ursodeoxycholic acid twice daily. A statistically significant improvement in all important hepatic parameters was achieved within 3 months of therapy. No further improvement could be observed once 6 months had elapsed. Significant decreases of SGOT (29.9 +/- 20.2 vs 17.7 +/- 7.1 U/l, p = 0.020), SGPT (43.8 +/- 31.0 vs. 19.6 +/- 6.7 U/l, p = 0.0012), GLDH (20.1 +/- 20.9 vs. 5.2 +/- 2.6 U/l, p = 0.0001) und gamma-GT (152.0 +/- 124.8 vs. 60.6 +/- 49.2 U/l, p = 0.0064) were observed during treatment. Despite tendential improvement, serum biliruhin, levels (18.2 +/- 9.4 vs. 16.9 +/- 9.4 mumol/l, p = 0.287) did not change significantly during treatment. Ursodeoxycholic acid may be beneficial in altering the natural course of chronic active hepatitis and of value in preventing mild attacks of immune hepatitis. The simple fact that ursodeoxycholic acid administration is essentially free of side-effects can go a long way towards justifying further clinically controlled studies.
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PMID:[Positive effect of ursodeoxycholic acid on liver enzymes in autoimmune hepatitis with little activity--a pilot study]. 908 12

The purpose of this study was to assess the relative incidence of chronic hepatitis in a population of patients with chronic liver disease and to determine the etiological spectrum of this syndrome with special reference to its defined histopathological forms. Histopathology aided by immunohistochemistry, and serology aided by the PCR method were employed in studies of liver biopsy specimens and serum samples, respectively. Out of 1150 patients with chronic liver disease examined, chronic hepatitis was diagnosed in 685 (60% of all cases examined). In this group, there were 308 males aged 18-74 yrs (mean 32 yrs), 153 females aged 18-71 yrs (mean 43 yrs), and 213 children aged 1-17 yrs (mean 8 yrs). Viral infections documented in these patients included HBV (50.4%), HCV (36.2%), HBV/HCV (7.2%) and HBV/HDV (0.7%); cryptogenic and autoimmune hepatitis (AIH) accounted for 2.9% and 2.6% all cases, respectively. In the group of minimal hepatitis (16.1%), HBV infection was documented in 66.4% of cases, HCV-in 29.1%, HBV/HCV-in 3.6% (one case of AIH was included into this group). In the group of mild hepatitis (44.2%), HBV infection accounted for 47.3% of cases, HCV-for 41.9%, HBV/HCV-for 9.9%, and 0.9% was diagnosed as cryptogenic. In the group of moderate hepatitis (19.6%), HBV infection accounted for 50% of cases, HCV-for 37.3%, and HBV/HCV-for 4.5%; cases of cryptogenic and AIH accounted for 3.7% and 4.5%, respectively. In the group of severe hepatitis (20.1%), HBV etiology was found in 44.9% of cases, HCV-in 28.3%, HBV/HCV-in 6.5% and HBV/HDV-in 3.6%; cryptogenic and AIH accounted for 6.5% and 8.0% of cases, respectively. There was a high incidence of low-titer autoantibodies (SMA, ANA and LKM) ranging from 75% in cryptogenic hepatitis and 51% in each HBV and HBV/HCV hepatitis to 46.3% in HCV hepatitis.
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PMID:[Etiology of chronic hepatitis as evaluated by liver biopsy and serum samples submitted to the Department of Immunopathology of the National Institute of Hygiene in 1993-1995]. 913 90

To determine the significance of antinuclear antibodies and their patterns of indirect immunofluorescence in type 1 autoimmune hepatitis, sera from 99 patients were evaluated. Patients with antinuclear antibodies had a lower frequency of liver transplantation (6% vs 22%, P = 0.04) than seronegative patients. They were also more commonly HLA-DR4-positive than seronegative patients (56% vs 30%, P = 0.05) and normal subjects (56% vs 30%, P = 0.004). The 42 patients with antinuclear antibodies and a diffuse pattern of indirect immunofluorescence had higher serum titers of ANA (serum titers > or = 1:500, 71% vs 14%, P < 0.0001) and SMA (serum titers > or = 1:500, 69% vs 27%, P = 0.003) than the 22 patients with antinuclear antibodies and a speckled pattern. These patients, however, were otherwise not distinguished by clinical features and treatment response. Patients with a speckled pattern had A1-B8-DR3 more frequently than patients with a diffuse pattern (65% vs 23%, P = 0.005) and normal subjects (65% vs 13%, P < 0.0001), but they had no other salient features. We conclude that patients with antinuclear antibodies have a better long-term prognosis than seronegative patients, and they have HLA-DR4 more commonly. The patterns of indirect immunofluorescence associated with ANA positivity have no practical clinical implications.
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PMID:Antinuclear antibodies and patterns of nuclear immunofluorescence in type 1 autoimmune hepatitis. 928 35

Antibodies to nuclei (ANA), smooth muscle (SMA), and liver/kidney microsomes type 1 (anti-LKM1) may occur in chronic hepatitis C. Distinct subspecificities, including ANA with the homogeneous pattern (ANA-H) and SMA with antiactin specificity (SMA-AA), are found in autoimmune hepatitis (AIH). This study was performed to characterize the hepatitis C virus (HCV)-associated autoantibodies and to evaluate their influence on the profile of the disease. Two hundred ninety consecutive patients with chronic hepatitis C and 35 control cases with AIH were screened for autoantibodies by indirect immunofluorescence (IFL) at 1:40 serum dilution. The ANA pattern was defined by IFL on HEp-2 cells and the SMA-AA identified by the presence of at least two of the following elements: 1) SMA(T) or SMA(G) pattern by IFL on kidney sections; 2) XR1 precipitating system by counterimmunoelectrophoresis; or 3) typical pattern by IFL on liver sections from phalloidin-intoxicated rats. ANA, SMA, and anti-LKM1 occurred in 9%, 20%, and 6% of chronic hepatitis C cases, respectively. The overall prevalence of autoantibodies was 30% (87 of 290). Compared with AIH, HCV-associated ANA and SMA exhibited ANA-H and SMA-AA at a lower prevalence (38% vs. 71%, P = .04 and 8% vs. 87%, P < .000001, respectively) and had a lower median titer (1:80 vs. 1:320, P < .001 and 1:40 vs. 1:320, P < .000001, respectively). The concomitant positivity for ANA-H and SMA-AA was detected in none of the HCV cases, but in 46% of AIH sera (P < .000001). Two parameters were independently associated with the autoantibodies in chronic hepatitis C: high alanine transaminase (ALT) serum levels (F = 14.04) and female gender (F = 5.03). At the univariate analysis, patients with autoantibodies had a more severe portal-periportal necroinflammation (median Scheuer's score: 2.05 vs. 1.64, P = .003). The presence of autoantibodies did not influence the response to interferon (IFN). In chronic hepatitis C, serum autoantibodies are common, but their subspecificities are distinct from those occurring in AIH. Whereas the absence of ANA-H and/or SMA-AA does not exclude AIH, the characterization of ANA and SMA may help to discriminate between the two conditions. As compared with the seronegative counterpart, autoantibody-positive chronic hepatitis C is more common in females and exhibits a more severe biochemical and histological activity. The response to IFN therapy, however, is similar.
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PMID:Serum autoantibodies in chronic hepatitis C: comparison with autoimmune hepatitis and impact on the disease profile. 958 9

Certain serum autoantibodies serve as useful diagnostic markers in AiLD; however, the etiology and pathogenesis of AiLD remain unknown. Although AiLD is characterized by the presence of autoantibodies and other humoral immune abnormalities, there is significant evidence that cell-mediated immune mechanisms are critical contributors to tissue injury in AiLD. The most sensitive and specific diagnostic immunologic marker for PBC is AMA. The availability of commercial kits that measure AMA directed against PDH-E2 (anti-M2) using ELISA may increase standardization of this test. AiH is characterized by the presence of ANA, SMA, and LKM. ANA are most commonly identified by IIFM using Hep-2 cells as substrate. IIFM is most commonly used to detect SMA and LKM, which, like AMA, can be identified using rodent (rat or mouse) combined kidney/stomach/liver tissue blocks as substrate. Most clinical laboratories with a capability to perform IIFMs therefore can identify the characteristic autoantibody patterns described in AiLD. As specific ELISAs become available, their widespread use in clinical laboratories also will facilitate the work-up of individuals with suspected AiLD.
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PMID:Autoimmune liver diseases. 931 70

HCV infection and interferon-alpha (IFN-alpha) therapy have been associated with autoimmunity. To assess whether chronic liver disease (CLD) due to HCV infection or its treatment with IFN-alpha cause autoimmune manifestations, the prevalence of tissue autoantibodies in 51 children with chronic HCV infection and 84 with other CLD was analysed by standard techniques. Sixty-five percent of patients with chronic HCV infection, 66% with chronic hepatitis B infection and 60% with Wilson's disease were positive for at least one autoantibody. In the 51 subjects with chronic HCV infection (29 treated with IFN-alpha, 22 untreated), tested on 165 occasions over a median of 9 months (range 5-42 months), autoantibodies to nuclei (ANA), smooth muscle (SMA), gastric parietal cell (GPC) and/or liver kidney microsomal type 1 (LKM-1) were similarly prevalent in treated and untreated patients (90% versus 68%, P = 0.12). Positivity for SMA was present in 67%, GPC in 32%, ANA in 10%, LKM-1 in 8% of cases. Treatment with IFN-alpha had to be suspended due to transaminase elevation in one SMA-positive, one ANA-positive but in three of four LKM-1-positive patients. Our results show that: (i) autoantibodies are common in viral-induced hepatitis and Wilson's disease; (ii) positivity for SMA, GPC, ANA is part of the natural course of chronic HCV infection, their prevalence being unaffected by IFN-alpha; and (iii) IFN-alpha should be used cautiously in the treatment of LKM-1/HCV-positive patients.
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PMID:Autoantibody prevalence in children with liver disease due to chronic hepatitis C virus (HCV) infection. 964 17

The immune system is able to recognize and neutralize potentially harmful agents, conferring to the organism resistance to infectious and malignant diseases. The authors have reviewed the literature and identified a group of substances able to enhance and/or reduce different immune functions, both in an experimental model and in occupational and environmental human exposure. The group includes several polyhalogenated hydrocarbons, particularly polychlorinated biphenyls, polybrominated biphenyls, tetrachloro-dibenzo-p-dioxin (TCDD), some metals like lead, cadmium and mercury, pesticides, i.e. dithiocarbamates and organotin compounds, organic solvents. The observed changes are usually slight and do not allow prognostic conclusion. In this study, the authors propose a 3-level rank of tests suitable for the immune evaluation of individuals occupationally exposed to xenobiotics, divided into three levels, as follows: tier 1: immunoglobulin classes (IgG, IgA, IgM), complement fractions (C3, C4), rheumatoid factor, and non-organ specific autoantibodies (AMA, SMA, ANA); CD3, CD4, CD8, CD57, CD20, HLA-DR; CD3/HLA-DR positive lymphocyte subsets; tier 2: determination of the mitotic response of peripheral blood lymphocytes to phytohaemoagglutinin, anti-CD3 monoclonal antibody, phorbol-myristate-acetate (PMA) and polyclonal immunoglobulin production after stimulation with pokeweed mitogen; tier 3: cytokine production with and without mitogen stimulation. The approach is "step by step" and assumes the need of a closely integrated and comparative evaluation of the findings obtained. The protocol could be used in research fields; moreover, some of the tests could be useful in the monitoring of persons exposed in the environment or in the workplace to immunotoxic substances or to biological agents.
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PMID:[Immunotoxicology in occupational and environmental medicine: prospectives, limitations, and research objectives]. 973 91

Autoimmune liver diseases comprise a number of disorders in which inflammatory damage to the liver is believed to derive from an autoimmune attack. These include autoimmune hepatitis (AIH), characterised by positive smooth muscle and/or nuclear (SMA/ANA) or liver kidney microsomal type 1 (LKM1) antibodies, autoimmune sclerosing cholangitis (ASC), usually SMA/ANA positive, and AIH after liver transplantation, which is positive for SMA, ANA, or atypical LKM. These disorders often present with symptoms indistinguishable from prolonged acute hepatitis. Less commonly the onset is insidious, with nonspecific symptoms, or with complications of portal hypertension. For AIH and ASC, experimental evidence suggests that usually in individuals genetically predisposed to autoimmunity, a liver self antigenic peptide is recognized by T lymphocytes which promote a cascade of autoaggressive processes. For AIH after liver transplantation, the pathogenic mechanisms remain to be elucidated. All types of autoimmune liver disorders appear to respond favourably to early treatment with prednisolone with or without azathioprine. For patients presenting with fulminant hepatic failure or with already advanced cirrhosis, immunosuppression is rarely effective and the only mode of treatment is liver transplantation. The role of other immunosuppressant or immunomodulatory drugs, like cyclosporin A, tacrolimus or ursodeoxycholic acid, in the treatment of autoimmune liver disorders remains to be defined.
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PMID:Immunological liver diseases in children. 977 27

Autoimmune hepatitis is a chronic inflammatory liver disorder of unknown etiology associated with serum autoantibodies and hypergammaglobulinemia. This disease has a broad spectrum of presentations ranging from asymptomatic to fulminant hepatic failure. A 36 year old female with past history of hypothyroidism developed jaundice 2 months prior to admission. Outpatient evaluation revealed ANA and anti-SMA antibodies in high titers, negative viral markers for hepatitis, and hypergammaglobulinemia. A presumptive diagnosis of autoimmune hepatitis was made; steroids were recommended but the patient did not take them. She was admitted to the University Hospital due to increased jaundice, general malaise and ascites 5 weeks later. She deteriorated developing coagulopathy, encephalopathy and increasing hyperbilirubinemia. Intravenous corticosteroids were started. The patient improved and was discharged 3 weeks after admission. Fulminant hepatic failure has a high mortality and may require liver transplant. Our patient survived fulminant hepatic failure that resolved after corticosteroid therapy. It is important to identify and distinguish autoimmune hepatitis from other forms of liver disease because of the high percentage of response to immuno-suppressive therapy. Early diagnosis and treatment of this condition could improve survival, quality of life, and defer liver transplantation.
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PMID:Steroid therapy in fulminant hepatic failure secondary to autoimmune hepatitis. 988 78


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