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Mitochondrial antigens as targets of cellular and humoral auto-immunity in primary biliary cirrhosis

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Abstract

Several factors point toward an auto-immune pathogenesis for primary biliary cirrhosis (PBC), mostly based on the presence of serum auto-antibodies to mitochondrial antigens (AMAs) and autoreactive T cells (both helper and cytotoxic). Interestingly, epitopes recognized by AMA and T-cell clones are located within overlapping areas of the antigens. Moreover, a role for an imbalance in cytokine pattern and for natural-killer lymphocytes has also been proposed. Despite several experimental reports, no clear evidence is available regarding the interaction of these factors leading to bile duct destruction. This article reviews the current reports regarding the auto-immune reaction against mitochondrial auto-antigens in PBC.

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References

  1. Talwalkar, J. A. and Lindor, K. D. (2003), Lancet 362, 53–61.

    Article  PubMed  CAS  Google Scholar 

  2. Pares, A. and Rodes, J. (2003), Clin Liver Dis 7, 779–794.

    Article  PubMed  Google Scholar 

  3. Gershwin, M. E. and Ansari, A. A., Mackay, I. R., et al. (2000), Immunol Rev 174, 210–225.

    Article  PubMed  CAS  Google Scholar 

  4. Yeaman, S. J., Kirby, J. A., and Jones, D. E. (2000), Immunol Rev 174, 238–249.

    Article  PubMed  CAS  Google Scholar 

  5. Worman, H. J. and Courvalin, J. C. (2003), Autoimmun Rev 2, 211–217.

    Article  PubMed  Google Scholar 

  6. Kita, H., Mackay, I. R., Van De Water, J., and Gershwin, M. E. (2001), Gastroenterology 120, 1485–1501.

    Article  PubMed  CAS  Google Scholar 

  7. Fukushima, N., Nalbandian, G., Van De Water, J., et al. (2002), Hepatology 36, 1383–1392.

    PubMed  CAS  Google Scholar 

  8. Kita, H., Matsumura, S., He, X. S., et al. (2002), J Clin Invest 109, 1231–1240.

    Article  PubMed  CAS  Google Scholar 

  9. Kita, H., Naidenko, O. V., Kronenberg, M., et al. (2002), Gastroenterology 123, 1031–1043.

    Article  PubMed  CAS  Google Scholar 

  10. Hashimoto, E., Lindor, K. D., Homburger, H. A., et al. (1993), Mayo Clin Proc 68, 1049–1055.

    PubMed  CAS  Google Scholar 

  11. Krams, S. M., Van de Water, J., Coppel, R. L., et al. (1990), Hepatology 12, 306–313.

    Article  PubMed  CAS  Google Scholar 

  12. Hoffmann, R. M., Pape, G. R., Spengler, U., et al. (1989), Clin Exp Immunol 76, 210–215.

    PubMed  CAS  Google Scholar 

  13. Meuer, S. C., Moebius, U., Manns, M. M., et al. (1988), Eur J Immunol 18, 1447–1452.

    Article  PubMed  CAS  Google Scholar 

  14. Yasoshima, M., Nakanuma, Y., Tsuneyama, K., Van de Water, J., and Gershwin, M. E. (1995), J Pathol 175, 319–325.

    Article  PubMed  CAS  Google Scholar 

  15. Yasoshima, M., Tsuneyama, K., Harada, K., Sasaki, M., Gershwin, M. E., and Naknuma, Y. (2000), J Pathol 190, 93–99.

    Article  PubMed  CAS  Google Scholar 

  16. Van de Water, J., Ansari, A., Prindiville, T., et al. (1995), J Exp Med 181, 723–733.

    Article  PubMed  Google Scholar 

  17. Shimoda, S., Nakamura, M., Ishibashi, H., Hayashida, K., and Niho, Y. (1995), J Exp Med 181, 1835–1845.

    Article  PubMed  CAS  Google Scholar 

  18. Ichiki, Y., Shimoda, S., Hara, H., et al. (1997), Hepatology 26, 728–733.

    PubMed  CAS  Google Scholar 

  19. Shimoda, S., Van de Water, J., Ansari, A., et al. (1998), J Clin Invest 102, 1831–1840.

    PubMed  CAS  Google Scholar 

  20. Shimoda, S., Nakamura, M., Ishibashi, H., et al. (2003), Gastroenterology 124, 1915–1925.

    Article  PubMed  CAS  Google Scholar 

  21. Moebius, U., Manns, M., Hess, G., Kober, G., Meyer zum Buschenfelde, K. H., and Meuer, S. C. (1990), Eur J Immunol 20, 889–896.

    Article  PubMed  CAS  Google Scholar 

  22. Tsai, S. L., Lai, M. Y., and Chen, D. S. (1996), Clin Exp Immunol 103, 99–104.

    Article  PubMed  CAS  Google Scholar 

  23. Kita, H., Lian, Z. X., Van de Water, J., et al. (2002), J Exp Med 195, 113–123.

    Article  PubMed  CAS  Google Scholar 

  24. Matsumura, S., Kita, H., He, X. S., et al. (2002), Hepatology 36, 1125–1134.

    Article  PubMed  CAS  Google Scholar 

  25. Surh, C. D., Coppel, R., and Gershwin, M. E. (1990), J Immunol 144, 3367–3374.

    PubMed  CAS  Google Scholar 

  26. Van de Water, J., Gershwin, M. E., Leung, P., Ansari, A., and Coppel, R. L. (1988), J Exp Med 167, 1791–1799.

    Article  PubMed  Google Scholar 

  27. Moteki, S., Leung, P. S., Dickson, E. R., et al. (1996), Hepatology 23, 436–444.

    Article  PubMed  CAS  Google Scholar 

  28. Leung, P. S., Chuang, D. T., Wynn, R., et al. (1995), Hepatology 22, 505–513.

    PubMed  CAS  Google Scholar 

  29. Dubel, L., Tanaka, A., Leung, P. S., et al. (1999), Hepatology 29, 1013–1018.

    Article  PubMed  CAS  Google Scholar 

  30. Jaume, J. C., Parry, S. L., Madec, A. M., Sonderstrup, G., and Baekkeskov, S. (2002), J Immunol 169, 665–672.

    PubMed  CAS  Google Scholar 

  31. Panina-Bordignon, P., Lang, R., Van Endert, P. M., et al. (1995), J Exp Med 181, 1923–1927.

    Article  PubMed  CAS  Google Scholar 

  32. Meinl, E. and Hohlfeld, R. (2002), Clin Exp Immunol 128, 395–397.

    Article  PubMed  CAS  Google Scholar 

  33. Kita, H., Kronenberg, M., Gershwin, M. E., In: Gershwin, M. E., Vierling, J. M., and Manns, M. P., eds. Liver Immunology. Philadelphia: Hanley & Belfus, 2002, pp. 85–98.

    Google Scholar 

  34. Harada, K., Isse, K., Tsuneyama, K., Ohta, H., and Nakanuma, Y. (2003), Liver Int 23, 94–100.

    Article  PubMed  Google Scholar 

  35. Harada, K., Van de Water, J., Leung, P. S., et al. (1997), Hepatology 25, 791–796.

    Article  PubMed  CAS  Google Scholar 

  36. Martinez, O. M., Villanueva, J. C., Gershwin, M. E., and Krams, S. M. (1995), Hepatology 21, 113–119.

    PubMed  CAS  Google Scholar 

  37. Shindo, M., Mullin, G. E., Braun-Elwert, L., Bergasa, N. V., Jones, E. A., and James, S. P. (1996), Clin Exp Immunol 105, 254–259.

    Article  PubMed  CAS  Google Scholar 

  38. Nagano, T., Yamamoto, K., Matsumoto, S., et al. (1999), J Clin Immunol 19, 422–427.

    Article  PubMed  CAS  Google Scholar 

  39. Lohr, H. F., Schlaak, J. F., Gerken, G., Fleischer, B., Dienes, H. P., and Meyer zum Buschenfelde, K. H. (1994), Liver 14, 161–166.

    PubMed  CAS  Google Scholar 

  40. Janeway, C. A., Jr. and Bottomly, K. (1994), Cell 76, 275–285.

    Article  PubMed  CAS  Google Scholar 

  41. Demetris, A. J. In: Sirica, A. E. and Longnecker, D. S., eds. Biliary and pancreatic epithelia. Pathobiology and Pathophysiology. New York: Marcel Dekker, 1997, pp. 127–180.

    Google Scholar 

  42. Tsuneyama, K., Van de Water, J., Leung, P. S., et al. (1995), Hepatology 21, 1031–1037.

    PubMed  CAS  Google Scholar 

  43. Nakanuma, Y. and Kono, N. (1991), Hum Pathol 22, 431–436.

    Article  PubMed  CAS  Google Scholar 

  44. Spengler, U., Leifeld, L., Braunschweiger, I., Dumoulin, F. L., Lechmann, M., and Sauerbruch, T. (1997), J Hepatol 26, 31–36.

    Article  PubMed  CAS  Google Scholar 

  45. Gaspari, A. A., Jenkins, M. K., and Katz, S. I. (1988), J Immunol 141, 2216–2220.

    PubMed  CAS  Google Scholar 

  46. Marelli-Berg, F. M. and Lechler, R. I. (1999), Immunol Rev 172, 297–314.

    Article  PubMed  CAS  Google Scholar 

  47. Leon, M. P., Bassendine, M. F., Wilson, J. L., Ali, S., Thick, M., and Kirby, J. A. (1996), Hepatology 24, 561–567.

    Article  PubMed  CAS  Google Scholar 

  48. Cruickshank, S. M., Southgate, J., Selby, P. J., and Trejdosiewicz, L. K. (1999), J Hepatol 31, 1026–1033.

    Article  PubMed  CAS  Google Scholar 

  49. Dienes, H. P., Lohse, A. W., Gerken, G., et al. (1997), Virchows Arch 431, 119–124.

    Article  PubMed  CAS  Google Scholar 

  50. Tsuneyama, K., Harada, K., Yasoshima, M., Kaji, K., Gershwin, M. E., and Nakanuma, Y. (1998), J Pathol 186, 126–130.

    Article  PubMed  CAS  Google Scholar 

  51. Markovic-Plese, S., Cortese, I., Wandinger, K. P., McFarland, H. F., and Martin, R. (2001), J Clin Invest. 108, 1185–1194.

    Article  PubMed  CAS  Google Scholar 

  52. Schirmer, M., Vallejo, A. N., Weyand, C. M. and Goronzy, J. J. (1998), J Immunol 161, 1018–1025.

    PubMed  CAS  Google Scholar 

  53. Vallejo, A. N., Schirmer, M., Weyand, C. M., and Goronzy, J. J. (2000), J Immunol 165, 6301–6307.

    PubMed  CAS  Google Scholar 

  54. Schmidt, D., Goronzy, J. J., and Weyand, C. M. (1996), J Clin Invest 97, 2027–2037.

    Article  PubMed  CAS  Google Scholar 

  55. Viglietta, V., Kent, S. C., Orban, T., and Hafler, D. A. (2002), J Clin Invest 109, 895–903.

    Article  PubMed  CAS  Google Scholar 

  56. Kamihira, T., Shimoda, S., Harada, K., et al. (2003), Gastroenterology 125, 1379–1387.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, TB192, Davis, CA

    Yasunori Ichiki, Carlo Selmi & M. Eric Gershwin

  2. Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan

    Shinji Shimoda

  3. Clinical Research Center, Nagasaki Medical Center, Kubara 2-1001-1, Omura, 856-8562, Nagasaki, Japan

    Hiromi Ishibashi

  4. Division of Gastroenterology/Hepatology, William Beaumont Hospital, Royal Oak, MI

    Stuart C. Gordon

Authors
  1. Yasunori Ichiki
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  2. Carlo Selmi
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  3. Shinji Shimoda
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  4. Hiromi Ishibashi
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  5. Stuart C. Gordon
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  6. M. Eric Gershwin
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Correspondence to M. Eric Gershwin.

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Ichiki, Y., Selmi, C., Shimoda, S. et al. Mitochondrial antigens as targets of cellular and humoral auto-immunity in primary biliary cirrhosis. Clinic Rev Allerg Immunol 28, 83–91 (2005). https://doi.org/10.1385/CRIAI:28:2:083

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