TY - JOUR
T1 - Antimitochondrial antibodies in kindreds of patients with primary biliary cirrhosis
T2 - Antimitochondrial antibodies are unique to clinical disease and are absent in asymptomatic family members
AU - Caldwell, Stephen H.
AU - Leung, Patrick S.C.
AU - Spivey, James R.
AU - Prindiville, Thomas
AU - de Medina, Maria
AU - Saicheur, Theparat
AU - Rowley, Merrill
AU - Reddy, K. Rajender
AU - Coppel, Ross
AU - Jeffers, Lennox J.
AU - MacKay, Ian R.
AU - Schiff, Eugene R.
AU - Gershwin, M. Eric
N1 - Copyright:
Copyright 2016 Elsevier B.V., All rights reserved.
PY - 1992/10
Y1 - 1992/10
N2 - 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 autoanti-bodies 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. These data do not support a deficiency of naturally occurring mitochondrial antibodies as an explanation for an inherited basis of the disease because none of our samples, patients or relatives, were positive for these putative autoantibodies. Among blood relatives, antimitochondrial antibodies were not detected in the absence of proved or suspected primary biliary cirrhosis. Within primary biliary cirrhosis kindreds, the presence of antimitochondrial antibodies should arouse suspicion of primary biliary cirrhosis even without overt clinical or biochemical disease markers.
AB - 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 autoanti-bodies 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. These data do not support a deficiency of naturally occurring mitochondrial antibodies as an explanation for an inherited basis of the disease because none of our samples, patients or relatives, were positive for these putative autoantibodies. Among blood relatives, antimitochondrial antibodies were not detected in the absence of proved or suspected primary biliary cirrhosis. Within primary biliary cirrhosis kindreds, the presence of antimitochondrial antibodies should arouse suspicion of primary biliary cirrhosis even without overt clinical or biochemical disease markers.
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U2 - 10.1002/hep.1840160408
DO - 10.1002/hep.1840160408
M3 - Article
C2 - 1398496
AN - SCOPUS:0026660952
VL - 16
SP - 899
EP - 905
JO - Hepatology
JF - Hepatology
SN - 0270-9139
IS - 4
ER -