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

AMA are detected in the serum of 92% to 95% of patients with PBC using indirect immunofluorescent methods. AIC is the term used to describe the 5% to 8% of AMA-negative PBC patients who uniformly have ANA and SMA. Recent applications of more sensitive and specific tests to detect serum AMA have shown that most, if not all, patients with AIC actually do have AMA. Emerging evidence that AMA and mitochondrial autoantigens play important roles in the immunopathogenesis of NSDC also suggests that AIC and PBC are likely to be a single disease, exhibiting variation in the types of autoantibodies and in both the concentrations and immunoglobulin isotypes of AMA.
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PMID:Primary biliary cirrhosis and autoimmune cholangiopathy. 1506

Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.
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PMID:Autoimmune hepatitis. 1572 81

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

Patients infected with schistosoma frequently show a high seroprevalence of anti-hepatitis C virus (anti-HCV) antibodies. The aim of this study was to find the underlying reason for this phenomenon, and to examine a possible involvement of autoantibodies. Out of 2,400 Egyptian blood donors, 192 (8%) were anti-HCV positive by ELISA. They were 133 males and 59 females with age ranging from 27 to 48 years. According to optical density ratio (ODR) of anti-HCV antibodies, 96 cases were low positive (LP) with ODR (1-2) designated as group I, and 96 were high positive (HP) with ODR (> or =2) (group II). Both groups were examined for quantitative HCV core antigen (HCVcAg), liver function (Albumin, ALT, AST) and anti-Schistosoma mansoni(anti-Sm) IgG. Group I cases were HCVcAg negative with normal liver function tests, and 44 of them were anti-Sm positive. Ninety cases (93.75%) of group II were HCVcAg positive with markedly affected liver function tests and 72 cases were anti-Sm positive. All group I cases were examined for autoimmune markers (ANA, AMA, SMA and LKM). In group I, 33 (75%) of anti-Sm positive cases were positive for one or more of the autoimmune markers examined, while none of anti-Sm negative was positive for any marker with significant difference between the two groups (P < 0.0001). Our results primarily on blood donors indicate that LP anti-HCV frequently represents false-positive reactivity with a possible role of Sm-induced autoantibodies in this phenomenon.
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PMID:Prevalence of low positive anti-HCV antibodies in blood donors: Schistosoma mansoni co-infection and possible role of autoantibodies. 1678 16

The anterior cingulate (AC) gyrus and the presupplementary motor area (pre-SMA) show pathological changes in Parkinson's disease (PD). We examined if PD patients show magnetic resonance spectroscopy (MRS) changes in NAA/Cr in the AC, pre-SMA, or posterior cingulate (PC). Forty-four (27 male, 17 female) healthy nondemented PD patients and 38 controls (18 male, 20 female) 65 years of age and older were examined using the Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental State Examination, Frontal Assessment Battery, and Geriatric Depression Scale. MRS was performed at 1.5 T. Voxels (8 cc; PRESS; TE = 80; TR = 1,600 ms) were placed mid-sagittally. Gray matter and white matter volumes were measured within voxels using SPM2. Spectra were analyzed using LC model to yield NAA/Cr and Cho/Cr. Demographic and cognitive measures did not differ between groups. Motor UPDRS was 17.7 +/- 8.8 for PD. Pre-SMA NAA/Cr was lower in PD (PD: 1.39 +/- 0.17; control: 1.47 +/- 0.16; P = 0.045) and correlated negatively with age (r = 0.39; P = 0.01), but not with UPDRS, disease duration, or dopamine equivalents. AC and PC NAA/Cr and Cho/Cr in any region did not differ (P > 0.05). In conclusion, pre-SMA NAA/Cr was selectively decreased in PD, consistent with neuronal dysfunction. This should be further examined as a biomarker of disease in PD.
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PMID:Magnetic resonance spectroscopic evidence for presupplementary motor area neuronal dysfunction in Parkinson's disease. 1721 52

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to the development of autoimmune phenomena is unclear. Whatever its etiology, the recognition of this potentially life-threatening syndrome is important since its management differs from that of standard anti-rejection therapy.
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PMID:Autoimmune paediatric liver disease. 1852 33

The conventional treatment of autoimmune hepatitis (AIH) in children, which includes prednisone alone or in combination with azathioprine, induces remission in most cases but is often associated with poorly tolerated side effects. To avoid the adverse effects, Alvarez et al. introduced an alternative treatment regimen, using cyclosporine A (CyA) as primary immunosuppression. We carried out a retrospective study to evaluate the efficacy and tolerance of CyA treatment in children and adolescents with AIH treated in our center. During 2000-2010 period, nine children (6 female) aged 5-17.5 years, were diagnosed with AIH according to established international criteria. Following the suggested protocol, CyA was administered orally and when the transaminases tended to normalise, dose was adjusted to lover serum levels. Conversion to low dose of prednisone and azathioprine was started after 6 months, with gradual tapering and discontinuation of CyA. All nine patient had elevated transaminases and gammaglobulin levels, with proven histological changes typical for AIH in 8 patients that underwent liver biopsy (in one patient biopsy was contraindicated due to the prolonged prothrombin time). Serum ANA/SMA autoantibodies were positive in all but one patient, who had positive anti-LKM1. Complete or near complete and persistent normalisation of transaminase activity was observed in 8/9 patients within first 6 to 12 months. In one patient with partial response, an overlap syndrome was established. After ursodeoxycholic acid was added complete remission was observed. All patients had excellent clinical course and histological improvement. During the long-term follow-up (1.5-9 yrs; median 4.5 yrs), biochemical relapse occured in one patient after discontinuation of maintenance corticosteroid dose. Despite registered improvement, none of the patients fulfilled the criteria for therapy discontinuation, so all of them are still receiving maintenance doses of prednisone or azathioprine. The applied protocol allowed for the control of the liver inflammatory disease in all of our patients and protected them from the side effects related to steroid treatment. Side effects of CyA were minimal and were well tolerated.
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PMID:Cyclosporine induced biochemical remission in childhood autoimmune hepatitis. 2321 60

Autoimmune hepatitis (AIH) is an inflammatory condition of the liver that has a multitude of clinical presentations from chronic hepatitis to acute fulminant hepatitis. AIH diagnosis is typically suspected after ruling out other causes of hepatitis (such as vial hepatitis, hemochromatosis, Wilson's disease, and primary biliary cirrhosis) through serological tests and by findings of high titers of certain autoantibodies (ANA and anti-SMA for type 1 AIH and anti-LKM-1 for type 2 AIH). AIH like most inflammatory conditions is associated with increased ferritin levels (acute-phase reactant) but typically near-normal transferrin saturation. The presence of excessive ferritin level in absence of high-transferrin saturation helps differentiate secondary iron overload from hemochromatosis where transferrin saturation is typically high. We herein describe a case of AIH that presented with high ferritin levels and transferrin saturation suggesting a diagnosis of hemochromatosis and needed arduous work-up to arrive at accurate diagnosis of AIH.
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PMID:Autoimmune hepatitis: diagnostic dilemma in the setting of suspected iron overload. 2402 49

Autoimmune hepatitis (AH) is a chronic inflammatory immunodependent disease of the liver. Women are affected more frequently than men. The patients show clinical and morphological signs of chronic hepatitis, extrahepatic manifestations of immune disorders (autoimmune thyroiditis, non-specific ulcerative colitis, vitiligo, diabetes mellitus, etc.), readily respond to glucocorticoid therapy have elevated levels of ALA, gamma-globulins (especially IgG), serum ANA, SMA, LKM or SLA antibodies. Untreated AH promotes rapid development of liver cirrhosis with 90% 10-year lethality. AH is diagnosed by exclusion and is of primary importance for clinical practice. The treatment is based on the use of immunosuppressors as a rule prescribed in addition to steroid therapy. It results in complete remission and normal life expectancy in 80% of the cases.
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PMID:[Autoimmune hepatitis]. 2443 58

Hepatitis C virus (HCV) infection has been related to self-reactivity, extrahepatic manifestations and autoimmune diseases. The main goals of this work were to study the prevalence of autoantibodies and their relationship with viral titers and biochemical markers of hepatic damage in patients infected with HCV. Autoantibodies (ANA, AMA, SMA, APC, LKM, DNAds, ANCA, ATG and RF) were determined in 73 individuals with chronic HCV infection and 44 healthy volunteers. The presence of these antibodies was related to demographic variables, viral titers and biochemical parameters. A high prevalence of autoantibodies, particularly for RF, that was associated with female gender was observed in HCV-infected patients. In addition, SMA, ANA and ATG showed increased frequencies in HCV infection. Interestingly, the concurrent detection of SMA and more than one autoantibody was associated with high gGT levels. Notably, concurrent higher gGT, HCV and SMA levels were observed in male patients as compared to their female counterparts. These results indicate a relationship between HCV infection and the concurrent detection of various autoantibodies in the absence of symptoms of autoimmune diseases. They also suggest a link among the presence of a variety of autoantibodies simultaneously with SMA, increased gGT levels and HCV titers in a population of male patients.
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PMID:High prevalence of a variety of autoantibodies in a population of hepatitis C virus-infected individuals. 2992 49


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