Antimitochondrial antibodies in kindreds of patients with primary biliary cirrhosis: Antimitochondrial antibodies are unique to clinical disease and are absent in asymptomatic family members

Stephen H. Caldwell, Patrick S Leung, James R. Spivey, Thomas P Prindiville, Maria De Medina, Theparat Saicheur, Merrill Rowley, K. Rajender Reddy, Ross Coppel, Lennox J. Jeffers, Ian R. Mackay, Eugene R. Schiff, M. Eric Gershwin

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)899-905
Number of pages7
JournalHepatology
Volume16
Issue number4
StatePublished - Oct 1992

Fingerprint

Biliary Liver Cirrhosis
Antibodies
Autoantigens
Spouses
Keto Acids
Indirect Fluorescent Antibody Technique
Immunoblotting
Liver Diseases
Siblings
Oxidoreductases
Enzymes
Dihydrolipoyllysine-Residue Acetyltransferase
Nuclear Antigens
Liver
Mitochondrial Proteins
Pruritus
Sarcoidosis
Autoantibodies
Fluorescent Antibody Technique
Alkaline Phosphatase

ASJC Scopus subject areas

  • Hepatology

Cite this

Antimitochondrial antibodies in kindreds of patients with primary biliary cirrhosis : Antimitochondrial antibodies are unique to clinical disease and are absent in asymptomatic family members. / Caldwell, Stephen H.; Leung, Patrick S; Spivey, James R.; Prindiville, Thomas P; De Medina, Maria; Saicheur, Theparat; Rowley, Merrill; Reddy, K. Rajender; Coppel, Ross; Jeffers, Lennox J.; Mackay, Ian R.; Schiff, Eugene R.; Gershwin, M. Eric.

In: Hepatology, Vol. 16, No. 4, 10.1992, p. 899-905.

Research output: Contribution to journalArticle

Caldwell, SH, Leung, PS, Spivey, JR, Prindiville, TP, De Medina, M, Saicheur, T, Rowley, M, Reddy, KR, Coppel, R, Jeffers, LJ, Mackay, IR, Schiff, ER & Gershwin, ME 1992, 'Antimitochondrial antibodies in kindreds of patients with primary biliary cirrhosis: Antimitochondrial antibodies are unique to clinical disease and are absent in asymptomatic family members', Hepatology, vol. 16, no. 4, pp. 899-905.
Caldwell, Stephen H. ; Leung, Patrick S ; Spivey, James R. ; Prindiville, Thomas P ; De Medina, Maria ; Saicheur, Theparat ; Rowley, Merrill ; Reddy, K. Rajender ; Coppel, Ross ; Jeffers, Lennox J. ; Mackay, Ian R. ; Schiff, Eugene R. ; Gershwin, M. Eric. / Antimitochondrial antibodies in kindreds of patients with primary biliary cirrhosis : Antimitochondrial antibodies are unique to clinical disease and are absent in asymptomatic family members. In: Hepatology. 1992 ; Vol. 16, No. 4. pp. 899-905.
@article{b0271e5adac34cdb98f9065d42304101,
title = "Antimitochondrial antibodies in kindreds of patients with primary biliary cirrhosis: Antimitochondrial antibodies are unique to clinical disease and are absent in asymptomatic family members",
abstract = "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.",
author = "Caldwell, {Stephen H.} and Leung, {Patrick S} and Spivey, {James R.} and Prindiville, {Thomas P} and {De Medina}, Maria and Theparat Saicheur and Merrill Rowley and Reddy, {K. Rajender} and Ross Coppel and Jeffers, {Lennox J.} and Mackay, {Ian R.} and Schiff, {Eugene R.} and Gershwin, {M. Eric}",
year = "1992",
month = "10",
language = "English (US)",
volume = "16",
pages = "899--905",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

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

AU - Spivey, James R.

AU - Prindiville, Thomas P

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

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.

UR - http://www.scopus.com/inward/record.url?scp=0026660952&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0026660952&partnerID=8YFLogxK

M3 - Article

C2 - 1398496

AN - SCOPUS:0026660952

VL - 16

SP - 899

EP - 905

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -