Comparative studies of antimitochondrial autoantibodies in sera and bile in primary biliary cirrhosis

Akiyoshi Nishio, Judith A Van de Water, Patrick S Leung, Ruth Joplin, James M. Neuberger, Jack Lake, Anna Björkland, Thomas H. Tötterman, Marion Peters, Howard J. Worman, Aftab A. Ansari, Ross L. Coppel, M. Eric Gershwin

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Abstract

Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by destruction of intrahepatic bile ducts. Although the pathogenesis of this disease is still unknown, high titers of antimitochondrial autoantibodies (AMA) have long been recognized in patient sera. However, little is known about the presence of AMA in bile. In this study, we investigated bile and sera from patients with PBC and healthy controls for the presence of AMA and mitochondrial autoantigens. AMA were detected in the bile of 17 of 19 patients (89.4%) with PBC; they were specifically directed against the pyruvate dehydrogenase complex (PDC-E2) in 15 of 19 patients (78.9%), to the branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 6 of 19 patients (31.6%), and to the 2- oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 1 of 19 patients (5.3%). In a comparative study of sera from the same patients, anti-PDC-E2 antibodies were found in 19 of 19 patients (100%), anti-BCOADC in 9 of 19 patients (47.3%), and anti-OGDC-E2 in 4 of 19 patients (21.1%) patients. AMA in bile were always found together with antibodies of corresponding specificities in the serum from the same patient. Immunoglobulin (Ig)A AMA were found in the bile of 9 of 19 patients (47.7%) with PBC; they were specifically directed against PDC-E2 in 8 of 19 patients (42.1%) and to BCOADC in 2 of 19 patients (10.5%). Epitope mapping of IgA anti-PDC-E2 antibodies indicated that, like serum autoantibodies, the immunodominant epitope is directed against the inner lipoyl domain of PDC-E2. The prevalence and antigen reactivity of IgA AMA in sera correlated completely with IgA AMA in bile. Autoantibodies against nuclear envelope pore proteins (gp210) were found in 1 of 8 (12.5%) sera of patients with PBC, but not in bile. Furthermore, and of particular interest, we detected the autoantigens, PDC-E2, OGDC-E2, and BCOADC-E2, in the bile of 12 of 19 patients (63.2%), 9 of 19 patients (47.4%), and 9 of 19 patients (47.4%), respectively; PDC-E2 was found in only 1 of 17 (5.9%) disease controls. Although the presence of AMA in bile may merely reflect the presence of these antibodies in sera, the simultaneous detection of mitochondrial autoantigens in bile suggests an increase of mitochondrial autoantigens at inflammatory sites. Such autoantigens, coupled with AMA, may augment the local immune response and disease progression.

Original languageEnglish (US)
Pages (from-to)1085-1089
Number of pages5
JournalHepatology
Volume25
Issue number5
StatePublished - 1997

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Biliary Liver Cirrhosis
Bile
Autoantibodies
Serum
Autoantigens
Ketoglutarate Dehydrogenase Complex
3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)
Immunoglobulin A
Antibodies
Dihydrolipoyllysine-Residue Acetyltransferase
Epitope Mapping
Intrahepatic Bile Ducts
Nuclear Pore
Immunodominant Epitopes
Porins
Antibody Specificity
Immune System Diseases

ASJC Scopus subject areas

  • Hepatology

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Comparative studies of antimitochondrial autoantibodies in sera and bile in primary biliary cirrhosis. / Nishio, Akiyoshi; Van de Water, Judith A; Leung, Patrick S; Joplin, Ruth; Neuberger, James M.; Lake, Jack; Björkland, Anna; Tötterman, Thomas H.; Peters, Marion; Worman, Howard J.; Ansari, Aftab A.; Coppel, Ross L.; Gershwin, M. Eric.

In: Hepatology, Vol. 25, No. 5, 1997, p. 1085-1089.

Research output: Contribution to journalArticle

Nishio, A, Van de Water, JA, Leung, PS, Joplin, R, Neuberger, JM, Lake, J, Björkland, A, Tötterman, TH, Peters, M, Worman, HJ, Ansari, AA, Coppel, RL & Gershwin, ME 1997, 'Comparative studies of antimitochondrial autoantibodies in sera and bile in primary biliary cirrhosis', Hepatology, vol. 25, no. 5, pp. 1085-1089.
Nishio, Akiyoshi ; Van de Water, Judith A ; Leung, Patrick S ; Joplin, Ruth ; Neuberger, James M. ; Lake, Jack ; Björkland, Anna ; Tötterman, Thomas H. ; Peters, Marion ; Worman, Howard J. ; Ansari, Aftab A. ; Coppel, Ross L. ; Gershwin, M. Eric. / Comparative studies of antimitochondrial autoantibodies in sera and bile in primary biliary cirrhosis. In: Hepatology. 1997 ; Vol. 25, No. 5. pp. 1085-1089.
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abstract = "Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by destruction of intrahepatic bile ducts. Although the pathogenesis of this disease is still unknown, high titers of antimitochondrial autoantibodies (AMA) have long been recognized in patient sera. However, little is known about the presence of AMA in bile. In this study, we investigated bile and sera from patients with PBC and healthy controls for the presence of AMA and mitochondrial autoantigens. AMA were detected in the bile of 17 of 19 patients (89.4{\%}) with PBC; they were specifically directed against the pyruvate dehydrogenase complex (PDC-E2) in 15 of 19 patients (78.9{\%}), to the branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 6 of 19 patients (31.6{\%}), and to the 2- oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 1 of 19 patients (5.3{\%}). In a comparative study of sera from the same patients, anti-PDC-E2 antibodies were found in 19 of 19 patients (100{\%}), anti-BCOADC in 9 of 19 patients (47.3{\%}), and anti-OGDC-E2 in 4 of 19 patients (21.1{\%}) patients. AMA in bile were always found together with antibodies of corresponding specificities in the serum from the same patient. Immunoglobulin (Ig)A AMA were found in the bile of 9 of 19 patients (47.7{\%}) with PBC; they were specifically directed against PDC-E2 in 8 of 19 patients (42.1{\%}) and to BCOADC in 2 of 19 patients (10.5{\%}). Epitope mapping of IgA anti-PDC-E2 antibodies indicated that, like serum autoantibodies, the immunodominant epitope is directed against the inner lipoyl domain of PDC-E2. The prevalence and antigen reactivity of IgA AMA in sera correlated completely with IgA AMA in bile. Autoantibodies against nuclear envelope pore proteins (gp210) were found in 1 of 8 (12.5{\%}) sera of patients with PBC, but not in bile. Furthermore, and of particular interest, we detected the autoantigens, PDC-E2, OGDC-E2, and BCOADC-E2, in the bile of 12 of 19 patients (63.2{\%}), 9 of 19 patients (47.4{\%}), and 9 of 19 patients (47.4{\%}), respectively; PDC-E2 was found in only 1 of 17 (5.9{\%}) disease controls. Although the presence of AMA in bile may merely reflect the presence of these antibodies in sera, the simultaneous detection of mitochondrial autoantigens in bile suggests an increase of mitochondrial autoantigens at inflammatory sites. Such autoantigens, coupled with AMA, may augment the local immune response and disease progression.",
author = "Akiyoshi Nishio and {Van de Water}, {Judith A} and Leung, {Patrick S} and Ruth Joplin and Neuberger, {James M.} and Jack Lake and Anna Bj{\"o}rkland and T{\"o}tterman, {Thomas H.} and Marion Peters and Worman, {Howard J.} and Ansari, {Aftab A.} and Coppel, {Ross L.} and Gershwin, {M. Eric}",
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T1 - Comparative studies of antimitochondrial autoantibodies in sera and bile in primary biliary cirrhosis

AU - Nishio, Akiyoshi

AU - Van de Water, Judith A

AU - Leung, Patrick S

AU - Joplin, Ruth

AU - Neuberger, James M.

AU - Lake, Jack

AU - Björkland, Anna

AU - Tötterman, Thomas H.

AU - Peters, Marion

AU - Worman, Howard J.

AU - Ansari, Aftab A.

AU - Coppel, Ross L.

AU - Gershwin, M. Eric

PY - 1997

Y1 - 1997

N2 - Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by destruction of intrahepatic bile ducts. Although the pathogenesis of this disease is still unknown, high titers of antimitochondrial autoantibodies (AMA) have long been recognized in patient sera. However, little is known about the presence of AMA in bile. In this study, we investigated bile and sera from patients with PBC and healthy controls for the presence of AMA and mitochondrial autoantigens. AMA were detected in the bile of 17 of 19 patients (89.4%) with PBC; they were specifically directed against the pyruvate dehydrogenase complex (PDC-E2) in 15 of 19 patients (78.9%), to the branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 6 of 19 patients (31.6%), and to the 2- oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 1 of 19 patients (5.3%). In a comparative study of sera from the same patients, anti-PDC-E2 antibodies were found in 19 of 19 patients (100%), anti-BCOADC in 9 of 19 patients (47.3%), and anti-OGDC-E2 in 4 of 19 patients (21.1%) patients. AMA in bile were always found together with antibodies of corresponding specificities in the serum from the same patient. Immunoglobulin (Ig)A AMA were found in the bile of 9 of 19 patients (47.7%) with PBC; they were specifically directed against PDC-E2 in 8 of 19 patients (42.1%) and to BCOADC in 2 of 19 patients (10.5%). Epitope mapping of IgA anti-PDC-E2 antibodies indicated that, like serum autoantibodies, the immunodominant epitope is directed against the inner lipoyl domain of PDC-E2. The prevalence and antigen reactivity of IgA AMA in sera correlated completely with IgA AMA in bile. Autoantibodies against nuclear envelope pore proteins (gp210) were found in 1 of 8 (12.5%) sera of patients with PBC, but not in bile. Furthermore, and of particular interest, we detected the autoantigens, PDC-E2, OGDC-E2, and BCOADC-E2, in the bile of 12 of 19 patients (63.2%), 9 of 19 patients (47.4%), and 9 of 19 patients (47.4%), respectively; PDC-E2 was found in only 1 of 17 (5.9%) disease controls. Although the presence of AMA in bile may merely reflect the presence of these antibodies in sera, the simultaneous detection of mitochondrial autoantigens in bile suggests an increase of mitochondrial autoantigens at inflammatory sites. Such autoantigens, coupled with AMA, may augment the local immune response and disease progression.

AB - Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by destruction of intrahepatic bile ducts. Although the pathogenesis of this disease is still unknown, high titers of antimitochondrial autoantibodies (AMA) have long been recognized in patient sera. However, little is known about the presence of AMA in bile. In this study, we investigated bile and sera from patients with PBC and healthy controls for the presence of AMA and mitochondrial autoantigens. AMA were detected in the bile of 17 of 19 patients (89.4%) with PBC; they were specifically directed against the pyruvate dehydrogenase complex (PDC-E2) in 15 of 19 patients (78.9%), to the branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 6 of 19 patients (31.6%), and to the 2- oxoglutarate dehydrogenase complex E2 (OGDC-E2) in 1 of 19 patients (5.3%). In a comparative study of sera from the same patients, anti-PDC-E2 antibodies were found in 19 of 19 patients (100%), anti-BCOADC in 9 of 19 patients (47.3%), and anti-OGDC-E2 in 4 of 19 patients (21.1%) patients. AMA in bile were always found together with antibodies of corresponding specificities in the serum from the same patient. Immunoglobulin (Ig)A AMA were found in the bile of 9 of 19 patients (47.7%) with PBC; they were specifically directed against PDC-E2 in 8 of 19 patients (42.1%) and to BCOADC in 2 of 19 patients (10.5%). Epitope mapping of IgA anti-PDC-E2 antibodies indicated that, like serum autoantibodies, the immunodominant epitope is directed against the inner lipoyl domain of PDC-E2. The prevalence and antigen reactivity of IgA AMA in sera correlated completely with IgA AMA in bile. Autoantibodies against nuclear envelope pore proteins (gp210) were found in 1 of 8 (12.5%) sera of patients with PBC, but not in bile. Furthermore, and of particular interest, we detected the autoantigens, PDC-E2, OGDC-E2, and BCOADC-E2, in the bile of 12 of 19 patients (63.2%), 9 of 19 patients (47.4%), and 9 of 19 patients (47.4%), respectively; PDC-E2 was found in only 1 of 17 (5.9%) disease controls. Although the presence of AMA in bile may merely reflect the presence of these antibodies in sera, the simultaneous detection of mitochondrial autoantigens in bile suggests an increase of mitochondrial autoantigens at inflammatory sites. Such autoantigens, coupled with AMA, may augment the local immune response and disease progression.

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