Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033774 (pruritus)
 14,546 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 2-oxo-acid dehydrogenase family of enzymes have been identified as the major mitochondrial autoantigens of primary biliary cirrhosis. Using immunoblotting, enzyme-linked immunosorbent assay and enzyme inhibition with both purified mitochondrial proteins and recombinant autoantigens, we have studied family members and spouses of patients with primary biliary cirrhosis for the presence of antimitochondrial antibodies. Antimitochondrial antibodies and other common autoantigens were also tested for by indirect immunofluorescence. This study included 27 index patients with primary biliary cirrhosis, 15 spouses and 48 first- and second-degree relatives. Overall, 7 relatives (11%) were positive for autoantibodies to nuclear and cytoplasmic antigens by indirect immunofluorescence against mouse liver and stomach sections. However, with immunofluorescence, the reactivity strictly paralleled that of antimitochondrial antibodies in only one of these (1:640)--a sibling with mild pruritus and a liver biopsy specimen diagnostic of primary biliary cirrhosis despite normal levels of serum alkaline phosphatase. In addition, one of the mothers, who had a history of sarcoidosis, was positive by immunoblotting for antibodies to the E2 subunit of the pyruvate dehydrogenase complex and protein X. All other relatives were negative for all of the assays. Antibodies to neither the 2-oxo-acid dehydrogenase enzymes nor the recently proposed family of naturally occurring mitochondrial antibodies were found in spouses or healthy relatives. Three other first-degree relatives suffered from liver disease: two died (one from primary biliary cirrhosis and the other from an unknown type of liver disease) and one (a sibling with primary biliary cirrhosis) was unavailable for testing. Our results are consistent with a familial predisposition to primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Antimitochondrial antibodies in kindreds of patients with primary biliary cirrhosis: antimitochondrial antibodies are unique to clinical disease and are absent in asymptomatic family members. 139 96

The most frequent and important symptoms in primary biliary cirrhosis (PBC) are pruritus and jaundice. In the majority, jaundice appears within one half to two years of onset of pruritus. Xanthoma, bone change and sicca syndrome are often observed. The recent increase in number of asymptomatic PBC is the result of progagation of medical examination. In the biochemical tests, elevation of the biliary enzymes, such as ALP and gamma-GTP, is characteristic, as well as, a high level of serum IgM. Serum bilirubin values are gradually raised along with the clinical course of the disease. Positive antimitochondrial antibody (AMA) is the most valuable immunological finding for the diagnosis of PBC. Anti-pyruvate dehydrogenase complex E2 component E2 has the same significance as AMA. Diagnostic criteria si shown in this paper.
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PMID:[Primary biliary cirrhosis: symptoms, laboratory data and diagnosis]. 811 1

Thomas Addison described three of the classical autoimmune diseases, so can justifiably be regarded as one of the fathers of the study of autoimmunity. The least well recognised of these conditions, the autoimmune liver disease primary biliary cirrhosis (PBC), is in some ways the most interesting. As a result of the relatively advanced state of knowledge of its immunopathogenesis, it represents a good model for the study of autoimmune disease. The classical pathological lesion of PBC is apoptotic damage to the biliary epithelial cells lining the small intrahepatic bile ducts. The disease is typified by two symptom sets: fatigue and pruritus, which can occur at any stage of the disease process, and the features of advanced liver disease, which occur when secondary liver damage results from bile retention. Although autoantibodies directed at, in particular, pyruvate dehydrogenase complex (PDC) are almost universally present in PBC (and represent an important diagnostic tool), it appears likely that CD8+ cytotoxic T cells reactive with self-PDC derived epitopes are directly responsible for target cell damage. Recent studies in humans and a novel murine disease model have shed light on the mechanism of breakdown of immune tolerance to self-PDC; they provide important insights into the pathogenesis of PBC in particular and of autoimmunity in general.
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PMID:Addison's other disease: primary biliary cirrhosis as a model autoimmune disease. 1293 51

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9-10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13-15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC.
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PMID:Primary biliary cirrhosis. 1960 70