Comparative immunoreactivity of anti-trifluoroacetyl (TFA) antibody and anti-lipoic acid antibody in primary biliary cirrhosis: Searching for a mimic

Motoko Sasaki, Aftab Ansari, Neil Pumford, Judith A Van de Water, Patrick S Leung, Ken M. Humphries, Luke I. Szweda, Yasuni Nakanuma, Thomas E. Roche, Ross L. Coppel, Jean Francois Bach, M. Eric Gershwin

Research output: Contribution to journalArticle

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Abstract

Previous studies documenting the existence of cross-reactivity between the lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2 [the major autoantigen in Primary biliary cirrhosis (PBC)] and trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to an initial insult with an environmental agent that cross-reacts with TFA. Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA antibody and anti-lipoic acid (LA) antibody against the mitochondrial autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non-lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2, TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast, anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC enzyme activity. Hence, although considerable cross reactivity exists between anti-TFA and anti-LA, the molecular nature of the interaction is clearly different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14 PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC and controls. However, anti-LA produced much stronger focalized staining of the bile ducts of diseased liver. This study suggests that while anti-TFA antibody recognizes lipoic acid-linked enzymes and proteins, the epitope recognized differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that a response to TFA is the triggering event in PBC. Anti-LA antibodies share a higher degree of similarity to PBC sera providing suggestive evidence that anti-LA antibodies or anti-LA like antibodies (mimotopes) may help define the initiator of the autoimmune response.

Original languageEnglish (US)
Pages (from-to)51-60
Number of pages10
JournalJournal of Autoimmunity
Volume15
Issue number1
DOIs
StatePublished - 2000

Fingerprint

Thioctic Acid
Biliary Liver Cirrhosis
Anti-Idiotypic Antibodies
Antibodies
dihydrolipoamide succinyltransferase
Autoantigens
Enzymes
Bile Duct Diseases
Serum
Staining and Labeling
Proteins
Bile Ducts
Autoimmunity

Keywords

  • Anti-mitochondrial autoantibody
  • Halothane
  • Lipoic acid
  • Liver
  • Primary biliary cirrhosis
  • Trifluoroacetylated protein

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Comparative immunoreactivity of anti-trifluoroacetyl (TFA) antibody and anti-lipoic acid antibody in primary biliary cirrhosis : Searching for a mimic. / Sasaki, Motoko; Ansari, Aftab; Pumford, Neil; Van de Water, Judith A; Leung, Patrick S; Humphries, Ken M.; Szweda, Luke I.; Nakanuma, Yasuni; Roche, Thomas E.; Coppel, Ross L.; Bach, Jean Francois; Gershwin, M. Eric.

In: Journal of Autoimmunity, Vol. 15, No. 1, 2000, p. 51-60.

Research output: Contribution to journalArticle

Sasaki, Motoko ; Ansari, Aftab ; Pumford, Neil ; Van de Water, Judith A ; Leung, Patrick S ; Humphries, Ken M. ; Szweda, Luke I. ; Nakanuma, Yasuni ; Roche, Thomas E. ; Coppel, Ross L. ; Bach, Jean Francois ; Gershwin, M. Eric. / Comparative immunoreactivity of anti-trifluoroacetyl (TFA) antibody and anti-lipoic acid antibody in primary biliary cirrhosis : Searching for a mimic. In: Journal of Autoimmunity. 2000 ; Vol. 15, No. 1. pp. 51-60.
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abstract = "Previous studies documenting the existence of cross-reactivity between the lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2 [the major autoantigen in Primary biliary cirrhosis (PBC)] and trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to an initial insult with an environmental agent that cross-reacts with TFA. Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA antibody and anti-lipoic acid (LA) antibody against the mitochondrial autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non-lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2, TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast, anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC enzyme activity. Hence, although considerable cross reactivity exists between anti-TFA and anti-LA, the molecular nature of the interaction is clearly different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14 PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC and controls. However, anti-LA produced much stronger focalized staining of the bile ducts of diseased liver. This study suggests that while anti-TFA antibody recognizes lipoic acid-linked enzymes and proteins, the epitope recognized differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that a response to TFA is the triggering event in PBC. Anti-LA antibodies share a higher degree of similarity to PBC sera providing suggestive evidence that anti-LA antibodies or anti-LA like antibodies (mimotopes) may help define the initiator of the autoimmune response.",
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AU - Sasaki, Motoko

AU - Ansari, Aftab

AU - Pumford, Neil

AU - Van de Water, Judith A

AU - Leung, Patrick S

AU - Humphries, Ken M.

AU - Szweda, Luke I.

AU - Nakanuma, Yasuni

AU - Roche, Thomas E.

AU - Coppel, Ross L.

AU - Bach, Jean Francois

AU - Gershwin, M. Eric

PY - 2000

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N2 - Previous studies documenting the existence of cross-reactivity between the lipoated (but not unlipoated) forms of the inner lipoyl domain (E2L2) of PDC-E2 [the major autoantigen in Primary biliary cirrhosis (PBC)] and trifluoroacetylated (TFA) proteins, led us to hypothesize that PBC may be due to an initial insult with an environmental agent that cross-reacts with TFA. Therefore, we performed a comparative study of the reactivity of rabbit anti-TFA antibody and anti-lipoic acid (LA) antibody against the mitochondrial autoantigens of human PBC and various TFA and LA conjugated proteins. Whereas both anti-TFA and anti-LA reacted with PDC-E2, the wild-type lipoated form of E2L2, OGDC-E2, E3-BP and LA-KLH, neither reacted with BCOADC-E2 or the non-lipoated form of E2L2. Of interest was that while anti-TFA reacted with PDC-E2, TFA-RSA and LA-KLH, it failed to inhibit PDC-E2 enzyme function. In contrast, anti-LA demonstrated cytoplasmic and mitochondrial staining, and inhibited PDC enzyme activity. Hence, although considerable cross reactivity exists between anti-TFA and anti-LA, the molecular nature of the interaction is clearly different. One of 14 PBC sera reacted weakly with TFA-albumin, whereas four of 14 PBC sera reacted with LA-KLH. Immunohistochemically, both anti-TFA and anti-LA antibodies reacted focally with periportal hepatocytes and bile ducts in both PBC and controls. However, anti-LA produced much stronger focalized staining of the bile ducts of diseased liver. This study suggests that while anti-TFA antibody recognizes lipoic acid-linked enzymes and proteins, the epitope recognized differs from that of anti-LA antibody and PBC autoantibodies. It is unlikely that a response to TFA is the triggering event in PBC. Anti-LA antibodies share a higher degree of similarity to PBC sera providing suggestive evidence that anti-LA antibodies or anti-LA like antibodies (mimotopes) may help define the initiator of the autoimmune response.

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