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18 Van de Water J, Ansari AA, Surh CD, Coppel RL, Roche T, Bonkovsky H, et al. Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response of primary biliary cirrhosis. J Immunol 1991; 146:89-94. A study of recognition of recombinant human PDC-E2 by T cells cloned from the liver of patients with PBC: the first demonstration of T-cell recognition of PDC-E2. This paper also describes detection of aberrant distribution of PDC-E2 on biliary epithelium of patients with PBC using a mouse monoclonal antibody.
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21 Shimoda S, Nakamura M, Ishibashi H, Hayashida K, Niho Y. HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: evidence for molecular mimicry in human autoimmune diseases. J Exp Med 1995; 181:1835-1845. Identification of immunodominant T-cell epitopes of PDC-E2 using cloned peripheral blood T cells from Japanese patients with PBC.
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23 Ballardini G, Mirakian R, Bianchi FB, Pisi E, Doniach D, Bottazzo GF. Aberrant expression of HLA-DR antigens on bile duct epithelium in primary biliary cirrhosis: relevance to pathogenesis. Lancet 1984; ii:1009-1011. This study demonstrated de novo expression of MHC class II antigens on biliary epithelium of patients with PBC, with the implication of a key role for aberrant expression of MHC class II in induction of autoimmunity. The role of MHC class II in immune cell recognition and destruction of biliary epithelium has still to be determined.
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24 Adams DH, Hubscher S, Shaw J, Johnson GD, Rothlien R, Neuberger JM. Increased expression of intercellular adhesion molecule-1 (ICAM-1) on bile ducts in primary biliary cirrhosis and primary sclerosing cholangitis. Hepatology 1991; 14:426-431.
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26 Ayres RCS, Neuberger JM, Shaw J, Joplin R, Adams RH. Intercellular adhesion molecule-1 and MHC antigens on human intrahepatic bile duct cells: effect of pro-inflammatory cytokines. Gut 1993; 34:125-129.
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27 Leon MP, Bassendine MF, Gibbs P, Thick M, Kirby JA. Immunogenicity of biliary epithelium: study of the adhesive interaction with lymphocytes. Gastroenterology 1997; 112:968-977.
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28 Saidman SL, Duquesnoy RJ, Zeevi A, Fung JJ, Starzl TE, Demetris AJ. Recognition of major histocompatibility complex antigens on cultured human biliary epithelial cells by alloreactive lymphocytes. Hepatology 1991; 13:239-246. Demonstration that normal human biliary epithelial cells can be induced to express MHC class II in vitro in response to incubation with pro-inflammatory cytokines.
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29
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Abnormal expression of the E2 component of pyruvate dehydrogenase complex on the luminal surface of biliary epithelium occurs before MHC Class II and BB1/B7 expression
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29 Tsuneyama K, Van de Water J, Leung PSC, Cha S, Nakanuma Y, Kaplan M, et al. Abnormal expression of the E2 component of pyruvate dehydrogenase complex on the luminal surface of biliary epithelium occurs before MHC Class II and BB1/B7 expression. Hepatology 1995; 21:1031-1037. A key paper in determining a possible significance for PDC-E2 in the immunopathology of PBC. Using sequential biopsy specimens it was determined that aberrant distribution of PDC-E2 on biliary epithelium precedes de novo expression of MHC class II or lymphocyte co-stimulatory molecules, implying that aberrant PDC-E2 is one of the earliest detectable abnormalities within the liver and may be intimately related to initiating events in PBC.
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30 Kaji K, Tsuneyama K, Nakanuma Y, Harada K, Sasaki M, Kaneko S, et al. B7-2 positive cells around interlobular bile ducts in primary biliary cirrhosis and chronic hepatitis C. J Gastroenterol Hepatol 1997; 12:507-512.
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31 Leon MP, Kirby JA, Gibbs P, Burt A, Bassendine MF. Immunogenicity of biliary epithelial cells - study of expression of B7 molecules. J Hepatol 1995; 22:591-595. In conflict with immunohistochemical studies [29,30], this study suggested that lymphocyte co-stimulatory molecules are not expressed by human BEC in vitro.
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Leon, M.P.1
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32 Joplin R, Wallace LL, Johnson GD, Lindsay JG, Yeaman SJ, Palmer JM, et al. Subcellular localization of pyruvate dehydrogenase dihydrolipoamide acetyltransferase in human intrahepatic biliary epithelial cells. J Pathol 1995; 176:381-390. In this study, antibodies to PDC-E2 were found to bind to antigen on the external aspect of the plasma membrane of BEC purified from patients with PBC but not controls. The data suggested a mechanism whereby BEC could become targets for immunological recognition.
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Joplin, R.1
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33 Joplin R, Wallace LL, Lindsay JG, Palmer JM, Yeaman SJ, Neuberger JM. The human biliary epithelial cell plasma membrane antigen in primary biliary cirrhosis: pyruvate dehydrogenase X? Gastroenterology 1997; 113:1727-1733. The plasma membrane antigen recognized by antibodies to PDC-E2 was characterized. No evidence was found for cross-reactivity at the B-cell level; AMA reacted only with PDC-E2 and PDC-E3bp. Only PDC-E3bp was associated with the plasma membrane.
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34 Krams S, Surh CD, Coppel RL, Ansari A, Ruebner B, Gershwin ME. Immunization of experimental animals with dihydrolipoamide acetyltransferase as a recombinant polypeptide generates mitochondrial antibodies but not primary biliary cirrhosis. Hepatology 1989; 9:411-416.
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35 Van de Water J, Gerson LB, Ferrell LD, Lake JR, Coppel RL, Batts K, et al. Immunohistochemical evidence of disease recurrence after liver transplantation for primary biliary cirrhosis. Hepatology 1996; 24:1079-1084. Another key paper in determining the possible significance of PDC-E2 in immunopathology. Aberrant PDC-E2 was determined in biopsy specimens of allografts from liver transplant recipients. Parallels are apparent with [29]; aberrant PDC-E2 may be the earliest detectable abnormality in the liver and may precede not only PBC but also recurrent PBC in liver allografts.
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36 Joplin R, Lindsay JG, Hubscher SG, Strain AJ, Neuberger JM. Distribution of dihydrolipoamide acetyltransferase (E2) in the liver and portal lymph nodes of patients with primary biliary cirrhosis: an immunohistochemical study. Hepatology 1991; 14:442-447. This paper records the observation that aberrant distribution of PDC-E2 in patients with PBC is not restricted to BEC but is also found in cells in the draining lymph nodes of the liver.
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37 Hubscher SG, Elias E, Buckels JA, Mayer DA, McMaster P, Neuberger JM. Primary biliary cirrhosis: histological evidence of disease recurrence after liver transplantation. J Hepatol 1993; 18:173-184.
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38 Dmetrewski J, Mayer AD, Hubscher SG, Neuberger JM. Histological recurrence of primary biliary cirrhosis after liver transplantation: effect of immunosuppression. J Hepatol 1996; 24:253-257. This paper supports the earlier suggestion of recurrence of PBC in the allograft and demonstrates that recurrence is enhanced in the presence of specific immunosuppressive regimens, suggesting a possible role for an infectious agent in immunopathological mechanisms.
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39 Hopf U, Stemerowicz R, Rodloff A, Galanos C, Moller B, Lobeck H, et al. Relation between Escherichia coli R (rough)-forms in gut, lipid A and primary biliary cirrhosis. Lancet 1989; ii:1421-1422.
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