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, Judy Van De Water, Patrick S.C. Leung, Ken M. Humphries, Luke I. Szweda, Yasuni Nakanuma, Thomas E. Roche, Ross L. Coppel, Jean Francois Bach, M. Eric Gershwin

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21 Scopus citations

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 - Jan 1 2000

Keywords

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

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Sasaki, M., Ansari, A., Pumford, N., Van De Water, J., Leung, P. S. C., Humphries, K. M., Szweda, L. I., Nakanuma, Y., Roche, T. E., Coppel, R. L., Bach, J. F., & Gershwin, M. E. (2000). Comparative immunoreactivity of anti-trifluoroacetyl (TFA) antibody and anti-lipoic acid antibody in primary biliary cirrhosis: Searching for a mimic. Journal of Autoimmunity, 15(1), 51-60. https://doi.org/10.1006/jaut.2000.0390