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  • 1990-1994  (2)
  • primary biliary cirrhosis  (2)
  • Sjogren's syndrome  (1)
  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of clinical immunology 11 (1991), S. 239-245 
    ISSN: 1573-2592
    Keywords: Antimitochondrial antibodies ; pyruvate dehydrogenase ; primary biliary cirrhosis ; autoimmunity ; autoantibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Antimitochondrial antibodies (AMA) may be detected in 95% of patients with primary biliary cirrhosis (PBC). The target autoantigens for the AMA were recently identified as four closely related metabolic enzymes located in the mitochondria. We have purified the pyruvate dehydrogenase (PDH) enzyme from bovine heart, showing that all PBC sera reacted with a 74-kd band. PDH was utilized to establish an ELISA assay for detecting the relevant antibodies. One hundred twelve of 120 sera from patients with PBC (95%) reacted with the PDH but none of the 201 control sera, including normal subjects and a panel of sera from other patients with liver diseases, showed similar reactivity. In 77% of the PBC sera the anti-PDH antibody isotype was identified as a combination of IgG and IgM, while in 18% only IgM was detected. In 5% of the sera the isotype was confined to IgG. PBC sera specifically inhibited the PDH enzyme activity. The enzyme inhibition correlated with the anti-PDH antibody titers. Thus, PDH seems to be one of the major target epitopes for AMA observed in sera of patients with PBC.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-2592
    Keywords: Sjogren's syndrome ; systemic lupus erythematosus (SLE) ; polymyositis ; scleroderma ; primary biliary cirrhosis ; antimitochondrial autoantibodies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Anti-pyruvate dehydrogenase (PDH) antibodies were determined in 1451 sera of patients with primary biliary cirrhosis (PBC) and several autoimmune rheumatic conditions by ELISA and immunoblotting. They were detected in sera of 93% of the patients with PBC (179 of 192 patients) in 60 of 277 (22%) patients with Sjogren's syndrome (SjS), 34 of 437 (8%) patients with scleroderma, 33 of 191 patients with SLE (17%), and 5 of 55 (10%) patients with rheumatoid arthritis (RA) but in none of the patients with polymyositis or the antiphospholipid syndrome. The ELISA studies were confirmed by immunoblots showing binding of autoimmune rheumatic sera to the same epitope (74 kd) of mitochondria that the PBC sera reacted with. The identical binding characteristics were also confirmed by protein competition assays with purified PDH. In 4 of 53 patients with SjS who were positive for anti-PDH, high titers as in PBC were detected. The anti-PDH antibodies in Sjogren's patients were associated with deranged liver function tests and extraglandular features but did not correlate with any other non-organ-specific antibody. Follow-up studies confirmed the association of the emergence of anti-PDH antibodies with defects in liver function tests. The antibodies were more prevalent in SLE and RA when they were associated with Sjogren's syndrome (30 and 18.8%, respectively). Among patients with different forms of scleroderma, anti-PDH antibodies were noted in subjects with systemic sclerosis, morphea, and Raynaud's phenomenon. The incidence was much more significant among patients with calcinosis, Raynaud's, esophageal dysmotility, sclerosis, and telangiectasia (CREST) (8/34), in whom antibodies were detected in 5 who had already developed PBC. The relationship among anti-PDH antibodies, PBC, and development of other autoimmune rheumatic conditions is discussed. It is proposed that the early detection of anti-PDH antibodies in patients with rheumatic conditions may predict the future development of PBC. This observation may have therapeutic implications.
    Type of Medium: Electronic Resource
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