All Title Author
Keywords Abstract


Epstein-Barr Virus as a Trigger of Autoimmune Liver Diseases

DOI: 10.1155/2012/987471

Full-Text   Cite this paper   Add to My Lib

Abstract:

The pathogenesis of autoimmune diseases includes a combination of genetic factors and environmental exposures including infectious agents. Infectious triggers are commonly indicated as being involved in the induction of autoimmune disease, with Epstein-Barr virus (EBV) being implicated in several autoimmune disorders. EBV is appealing in the pathogenesis of autoimmune disease, due to its high prevalence worldwide, its persistency throughout life in the host’s B lymphocytes, and its ability to alter the host’s immune response and to inhibit apoptosis. However, the evidence in support of EBV in the pathogenesis varies among diseases. Autoimmune liver diseases (AiLDs), including autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC), have a potential causative link with EBV. The data surrounding EBV and AiLD are scarce. The lack of evidence surrounding EBV in AiLD may also be reflective of the rarity of these conditions. EBV infection has also been linked to other autoimmune conditions, which are often found to be concomitant with AiLD. This paper will critically examine the literature surrounding the link between EBV infection and AiLD development. The current evidence is far from being conclusive of the theory of a link between EBV and AiLD. 1. Introduction Several viruses have been considered to be triggers of autoimmunity and overt autoimmune disease [1–6]. Amongst those, Epstein-Barr virus (EBV), which is the cause of infectious mononucleosis, is unique in a sense as it has been implicated in the induction of multiple autoimmune diseases [7, 8]. These include systemic lupus erythematosus (SLE), multiple sclerosis (MS), autoimmune thyroiditis (AT), rheumatoid arthritis (RA), inflammatory bowel diseases (IBD), insulin-dependent diabetes mellitus (IDDM), Sj?gren’s syndrome (SjS), systemic sclerosis (SSc), myasthenia gravis, and autoimmune liver diseases (AiLD) [7–20]. In fact, there are very few autoimmune diseases in which EBV has not been considered as a potential trigger of immune-mediated destruction. While in some of these diseases there is growing evidence in support of the link between EBV and autoimmunity, the link is not as strong as in others, and the pathogenic involvement of EBV is a matter of heated debate. This paper will discuss the clinical and experimental data investigating the role of EBV in the pathogenesis of AiLD. As these diseases frequently co-occur with extrahepatic autoimmune diseases, we also discuss EBV’s involvement in the pathogenesis of autoimmune manifestations seen in

References

[1]  J. F. Bach, “Infections and autoimmune diseases,” Journal of Autoimmunity, vol. 25, supplement, pp. 74–80, 2005.
[2]  O. Barzilai, M. Ram, and Y. Shoenfeld, “Viral infection can induce the production of autoantibodies,” Current Opinion in Rheumatology, vol. 19, no. 6, pp. 636–643, 2007.
[3]  O. Barzilai, Y. Sherer, M. Ram, D. Izhaky, J. M. Anaya, and Y. Shoenfeld, “Epstein-Barr virus and cytomegalovirus in autoimmune diseases: are they truly notorious? a preliminary report,” Annals of the New York Academy of Sciences, vol. 1108, pp. 567–577, 2007.
[4]  A. M. Ercolini and S. D. Miller, “The role of infections in autoimmune disease,” Clinical and Experimental Immunology, vol. 155, no. 1, pp. 1–15, 2009.
[5]  S. Kivity, N. Agmon-Levin, M. Blank, and Y. Shoenfeld, “Infections and autoimmunity—friends or foes?” Trends in Immunology, vol. 30, no. 8, pp. 409–414, 2009.
[6]  V. Pordeus, M. Szyper-Kravitz, R. A. Levy, N. M. Vaz, and Y. Shoenfeld, “Infections and autoimmunity: a panorama,” Clinical Reviews in Allergy and Immunology, vol. 34, no. 3, pp. 283–299, 2008.
[7]  D. N. Posnett, “Herpesviruses and autoimmunity,” Current Opinion in Investigational Drugs, vol. 9, no. 5, pp. 505–514, 2008.
[8]  é. Toussirot and J. Roudier, “Epstein-Barr virus in autoimmune diseases,” Best Practice and Research: Clinical Rheumatology, vol. 22, no. 5, pp. 883–896, 2008.
[9]  J. A. James, K. M. Kaufman, A. D. Farris, E. Taylor-Albert, T. J. A. Lehman, and J. B. Harley, “An increased prevalence of Epstein-Barr virus infection in young patients suggests a possible etiology for systemic lupus erythematosus,” Journal of Clinical Investigation, vol. 100, no. 12, pp. 3019–3026, 1997.
[10]  A. S. Evans, “E. B. virus antibody in systemic lupus erythematosus,” Lancet, vol. 1, no. 7707, pp. 1023–1024, 1971.
[11]  A. S. Evans, N. F. Rothfield, and J. C. Niederman, “Raised antibody titres to E. B. virus in systemic lupus erythematosus,” Lancet, vol. 1, no. 7691, pp. 167–168, 1971.
[12]  B. D. Poole, R. H. Scofield, J. B. Harley, and J. A. James, “Epstein-Barr virus and molecular mimicry in systemic lupus erythematosus,” Autoimmunity, vol. 39, no. 1, pp. 63–70, 2006.
[13]  B. J. Harley, I. T. W. Harley, J. M. Guthridge, and J. A. James, “The curiously suspicious: a role for Epstein-Barr virus in lupus,” Lupus, vol. 15, no. 11, pp. 768–777, 2006.
[14]  K. H. Costenbader and E. W. Karlson, “Epstein-Barr virus and rheumatoid arthritis: is there a link?” Arthritis Research and Therapy, vol. 8, no. 1, p. 204, 2006.
[15]  L. I. Levin, K. L. Munger, M. V. Rubertone et al., “Multiple sclerosis and Epstein-Barr virus,” Journal of the American Medical Association, vol. 289, no. 12, pp. 1533–1536, 2003.
[16]  S. Haahr and P. H?llsberg, “Multiple sclerosis is linked to Epstein-Barr virus infection,” Reviews in Medical Virology, vol. 16, no. 5, pp. 297–310, 2006.
[17]  E. Y. Padalko and X. Bossuyt, “Anti-dsdna antibodies associated with acute ebv infection in sj?gren's syndrome,” Annals of the Rheumatic Diseases, vol. 60, no. 10, p. 992, 2001.
[18]  M. Trimeche, S. Ziadi, K. Amara et al., “Prevalence ofEpstein-Barr virus insj?gren's syndrome intunisia,” Revue De Medecine Interne, vol. 27, no. 7, pp. 519–523, 2006.
[19]  J. Vrbikova, I. Janatkova, V. Zamrazil, R. Tomiska, and T. Fucikova, “Epstein-Barr virus serology in patients with autoimmune thyroiditis,” Experimental and Clinical Endocrinology and Diabetes, vol. 104, no. 1, pp. 89–92, 1996.
[20]  S. Vento, L. Guella, F. Mirandola et al., “Epstein-Barr virus as a trigger for autoimmune hepatitis in susceptible individuals,” Lancet, vol. 346, no. 8975, pp. 608–609, 1995.
[21]  K. M. Pollard, “Gender differences in autoimmunity associated with exposure to environmental factors,” Journal of Autoimmunity, vol. 38, no. 2-3, pp. J177–J186, 2012.
[22]  D. Smyk, E. I. Rigopoulou, H. Baum, A. K. Burroughs, D. Vergani, and D. P. Bogdanos, “Autoimmunity and environment: am i at risk?” Clinical Reviews in Allergy and Immunology, pp. 1–14, 2011.
[23]  D. L. Jacobson, S. J. Gange, N. R. Rose, and N. M. H. Graham, “Epidemiology and estimated population burden of selected autoimmune diseases in the united states,” Clinical Immunology and Immunopathology, vol. 84, no. 3, pp. 223–243, 1997.
[24]  R. D. G. Leslie and M. Hawa, “Twin studies in auto-immune disease,” Acta Geneticae Medicae Et Gemellologiae, vol. 43, no. 1-2, pp. 71–81, 1994.
[25]  C. Selmi, M. J. Mayo, N. Bach et al., “Primary biliary cirrhosis in monozygotic and dizygotic twins: genetics, epigenetics, and environment,” Gastroenterology, vol. 127, no. 2, pp. 485–492, 2004.
[26]  G. S. Cooper, J. Wither, S. Bernatsky et al., “Occupational and environmental exposures and risk of systemic lupus erythematosus: silica, sunlight, solvents,” Rheumatology, vol. 49, no. 11, Article ID keq214, pp. 2172–2180, 2010.
[27]  P. Jarvinen and K. Aho, “Twin studies in rheumatic disease,” Seminars in Arthritis and Rheumatism, vol. 24, no. 1, pp. 19–28, 1994.
[28]  D. P. Bogdanos, D. S. Smyk, E. I. Rigopoulou, M. A Heneghan, C. Selmi, and M. E. Gershwin, “Twin studies in autoimmune disease: genetics, gender and environment,” Journal of Autoimmunity, vol. 38, no. 2-3, pp. J156–J169, 2012.
[29]  U. Christen, E. Hintermann, M. Holdener, and M. G. von Herrath, “Viral triggers for autoimmunity: is the 'glass of molecular mimicry' half full or half empty?” Journal of Autoimmunity, vol. 34, no. 1, pp. 38–44, 2010.
[30]  D. P. Bogdanos, M. Lenzi, M. Okamoto et al., “Multiple viral/self immunological cross-reactivity in liver kidney microsomal antibody positive hepatitis C virus-infected patients is associated with the possession of HLA B51,” International Journal of Immunopathology and Pharmacology, vol. 17, no. 1, pp. 83–92, 2004.
[31]  D. P. Bogdanos and I. G. McFarlane, “Cytochrome P450 2A6 meets P450 2D6: an enigma of viral infections and autoimmunity,” Journal of Hepatology, vol. 39, no. 5, pp. 860–863, 2003.
[32]  A. Lleo, C. Selmi, P. Invernizzi, M. Podda, and M. E. Gershwin, “The consequences of apoptosis in autoimmunity,” Journal of Autoimmunity, vol. 31, no. 3, pp. 257–262, 2008.
[33]  A. Alunno, E. Bartoloni, G. Nocentini et al., “Role of regulatory t cells in rheumatoid arthritis: facts and hypothesis,” Autoimmunity Highlights, vol. 1, no. 1, pp. 45–51, 2010.
[34]  G. Lettre and J. D. Rioux, “Autoimmune diseases: insights from genome-wide association studies,” Human Molecular Genetics, vol. 17, no. 2, pp. R116–121, 2008.
[35]  M. Gourley and F. W. Miller, “Mechanisms of disease: environmental factors in the pathogenesis of rheumatic disease,” Nature Clinical Practice Rheumatology, vol. 3, no. 3, pp. 172–180, 2007.
[36]  M. P. Pender, “Infection of autoreactive b lymphocytes with ebv, causing chronic autoimmune diseases,” Trends in Immunology, vol. 24, no. 11, pp. 584–588, 2003.
[37]  D. A. Thorley-Lawson, “Epstein-Barr virus: exploiting the immune system,” Nature Reviews Immunology, vol. 1, no. 1, pp. 75–82, 2001.
[38]  C. Garzelli, F. E. Taub, J. E. Scharff, B. S. Prabhakar, F. Ginsberg-Fellner, and A. L. Notkins, “Epstein-Barr virus-transformed lymphocytes produce monoclonal autoantibodies that react with antigens in multiple organs,” Journal of Virology, vol. 52, no. 2, pp. 722–725, 1984.
[39]  M. P. Manns, A. J. Czaja, J. D. Gorham et al., “Diagnosis and management of autoimmune hepatitis,” Hepatology, vol. 51, no. 6, pp. 2193–2213, 2010.
[40]  D. Vergani, M. S. Longhi, D. P. Bogdanos, Y. Ma, and G. Mieli-Vergani, “Autoimmune hepatitis,” Seminars in Immunopathology, vol. 31, no. 3, pp. 421–435, 2009.
[41]  G. Mieli-Vergani and D. Vergani, “Autoimmune hepatitis in children,” Clinics in Liver Disease, vol. 6, no. 3, pp. 335–346, 2002.
[42]  G. Mieli-Vergani and D. Vergani, “Autoimmune liver disease in children,” Annals of the Academy of Medicine Singapore, vol. 32, no. 2, pp. 239–243, 2003.
[43]  G. Mieli-Vergani and D. Vergani, “Autoimmune paediatric liver disease,” World Journal of Gastroenterology, vol. 14, no. 21, pp. 3360–3367, 2008.
[44]  G. Mieli-Vergani and D. Vergani, “Autoimmune hepatitis in children: what is different from adult aih?” Seminars in Liver Disease, vol. 29, no. 3, pp. 297–306, 2009.
[45]  M. S. Longhi, Y. Ma, G. Mieli-Vergani, and D. Vergani, “Aetiopathogenesis of autoimmune hepatitis,” Journal of Autoimmunity, vol. 34, no. 1, pp. 7–14, 2010.
[46]  D. Vergani, K. Choudhuri, D. P. Bogdanos, and G. Mieli-Vergani, “Pathogenesis of autoimmune hepatitis,” Clinics in Liver Disease, vol. 6, no. 3, pp. 439–449, 2002.
[47]  D. Vergani and G. Mieli-Vergani, “Aetiopathogenesis of autoimmune hepatitis,” World Journal of Gastroenterology, vol. 14, no. 21, pp. 3306–3312, 2008.
[48]  D. P. Bogdanos, P. Invernizzi, I. R. Mackay, and D. Vergani, “Autoimmune liver serology: current diagnostic and clinical challenges,” World Journal of Gastroenterology, vol. 14, no. 21, pp. 3374–3387, 2008.
[49]  D. P. Bogdanos, G. Mieli-Vergani, and D. Vergani, “Autoantibodies and their antigens in autoimmune hepatitis,” Seminars in Liver Disease, vol. 29, no. 3, pp. 241–253, 2009.
[50]  D. Vergani and G. Mieli-Vergani, “Pharmacological management of autoimmune hepatitis,” Expert Opinion on Pharmacotherapy, vol. 12, no. 4, pp. 607–613, 2011.
[51]  M. P. Manns and D. Vergani, “Autoimmune hepatitis,” Seminars in Liver Disease, vol. 29, no. 3, pp. 239–240, 2009.
[52]  M. S. Longhi, M. J. Hussain, R. R. Mitry et al., “Functional study of CD4+CD25+ regulatory t cells in health and autoimmune hepatitis,” Journal of Immunology, vol. 176, no. 7, pp. 4484–4491, 2006.
[53]  M. S. Longhi, Y. Ma, D. P. Bogdanos, P. Cheeseman, G. Mieli-Vergani, and D. Vergani, “Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease,” Journal of Hepatology, vol. 41, no. 1, pp. 31–37, 2004.
[54]  M. S. Longhi, Y. Ma, R. R. Mitry et al., “Effect of CD4(+)CD25(+) regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis,” Journal of Autoimmunity, vol. 25, no. 1, pp. 63–71, 2005.
[55]  M. S. Longhi, R. R. Mitry, M. Samyn et al., “Vigorous activation of monocytes in juvenile autoimmune liver disease escapes the control of regulatory T-cells,” Hepatology, vol. 50, no. 1, pp. 130–142, 2009.
[56]  A. Aceti, M. S. Mura, S. Babudieri, and S. A. Bacciu, “A young woman with hepatitis after a sore throat,” Lancet, vol. 346, no. 8990, p. 1603, 1995.
[57]  K. Kojima, R. Nagayama, S. Hirama et al., “Epstein-Barr virus infection resembling autoimmune hepatitis with lactate dehydrogenase and alkaline phosphatase anomaly,” Journal of Gastroenterology, vol. 34, no. 6, pp. 706–712, 1999.
[58]  V. Nobili, D. Comparcola, M. R. Sartorelli, R. Devito, and M. Marcellini, “Autoimmune hepatitis type 1 after Epstein-Barr virus infection,” Pediatric Infectious Disease Journal, vol. 22, no. 4, p. 387, 2003.
[59]  T. Chiba, S. Goto, O. Yokosuka et al., “Fatal chronic active Epstein-Barr virus infection mimicking autoimmune hepatitis,” European Journal of Gastroenterology and Hepatology, vol. 16, no. 2, pp. 225–228, 2004.
[60]  S. Nakajima, H. Umebayashi, R. Kurosawa et al., “A case of autoimmune hepatitis needed to be differentiated from ebv hepatitis, in that the histology of liver biopsy specimen was useful for diagnosis,” Nihon Rinsho Men'eki Gakkai Kaishi, vol. 28, no. 3, pp. 154–158, 2005.
[61]  D Cabibi, “Autoimmune hepatitis following Epstein-Barr virus infection,” BMJ Case Reports, vol. 2008, p. bcr0620080071, 2008.
[62]  M. M. Kaplan and M. E. Gershwin, “Primary biliary cirrhosis,” New England Journal of Medicine, vol. 353, no. 12, pp. 1261–1273, 2005.
[63]  S. Hohenester, R. P. J. Oude-Elferink, and U. Beuers, “Primary biliary cirrhosis,” Seminars in Immunopathology, vol. 31, no. 3, pp. 283–307, 2009.
[64]  J. Neuberger, “Primary biliary cirrhosis,” Lancet, vol. 350, no. 9081, pp. 875–879, 1997.
[65]  O. E. W. James, R. Bhopal, D. Howel, J. Gray, A. D. Burt, and J. V. Metcalf, “Primary biliary cirrhosis once rare, now common in the united kingdom?” Hepatology, vol. 30, no. 2, pp. 390–394, 1999.
[66]  W. R. Kim, K. D. Lindor, G. R. Locke et al., “Epidemiology and natural history of primary biliary cirrhosis in a u.s. community,” Gastroenterology, vol. 119, no. 6, pp. 1631–1636, 2000.
[67]  S. Sood, P. J. Gow, J. M. Christie, and P. W. Angus, “Epidemiology of primary biliary cirrhosis in victoria, australia: high prevalence in migrant populations,” Gastroenterology, vol. 127, no. 2, pp. 470–475, 2004.
[68]  H. Rautiainen, V. Salomaa, S. Niemela, et al., “Prevalence and incidence of primary biliary cirrhosis are increasing in Finland,” Scandinavian Journal of Gastroenterology, vol. 42, no. 11, pp. 1347–1353, 2007.
[69]  D. P. Bogdanos, H. Baum, and D. Vergani, “Antimitochondrial and other autoantibodies,” Clinics in Liver Disease, vol. 7, no. 4, pp. 759–777, 2003.
[70]  P. Pavlidis, M. G. Mytilinaiou, D. Roggenbuck, K. Conrad, A. Forbes, and D. P. Bogdanos, “Pancreatic GP2-specific autoantibodies are markers of crohn's disease,” Gut, vol. 60, supplement, pp. A212–A213, 2011.
[71]  C. D?hnrich, A. Pares, L. Caballeria et al., “New elisa for detecting primary biliary cirrhosis-specific antimitochondrial antibodies,” Clinical Chemistry, vol. 55, no. 5, pp. 978–985, 2009.
[72]  H. Liu, G. L. Norman, Z. Shums et al., “Pbc screen: an igg/iga dual isotype elisa detecting multiple mitochondrial and nuclear autoantibodies specific for primary biliary cirrhosis,” Journal of Autoimmunity, vol. 35, no. 4, pp. 436–442, 2010.
[73]  S. Hannam, D. P. Bogdanos, E. T. Davies et al., “Neonatal liver disease associated with placental transfer of anti-mitochondrial antibodies,” Autoimmunity, vol. 35, no. 8, pp. 545–550, 2002.
[74]  E. I. Rigopoulou, E. T. Davies, D. P. Bogdanos et al., “Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary biliary cirrhosis,” Liver International, vol. 27, no. 9, pp. 1226–1231, 2007.
[75]  D. Vergani and D. P. Bogdanos, “Positive markers in AMA-negative PBC,” American Journal of Gastroenterology, vol. 98, no. 2, pp. 241–243, 2003.
[76]  L. Wen, Y. Ma, D. P. Bogdanos et al., “Pédiatrie autoimmune liver diseases: the molecular basis of humoral and cellular immunity,” Current Molecular Medicine, vol. 1, no. 3, pp. 379–389, 2001.
[77]  P. Invernizzi, A. Lleo, and M. Podda, “Interpreting serological tests in diagnosing autoimmune liver diseases,” Seminars in Liver Disease, vol. 27, no. 2, pp. 161–172, 2007.
[78]  E. I. Rigopoulou, D. P. Bogdanos, C. Liaskos et al., “Anti-mitochondrial antibody immunofluorescent titres correlate with the number and intensity of immunoblot-detected mitochondrial bands in patients with primary biliary cirrhosis,” Clinica Chimica Acta, vol. 380, no. 1-2, pp. 118–121, 2007.
[79]  J. V. Metcalf, H. C. Mitchison, J. M. Palmer, D. E. Jones, M. F. Bassendine, and O. F. W. James, “Natural history of early primary biliary cirrhosis,” Lancet, vol. 348, no. 9039, pp. 1399–1402, 1996.
[80]  J. C. Courvalin and H. J. Worman, “Nuclear envelope protein autoantibodies in primary biliary cirrhosis,” Seminars in Liver Disease, vol. 17, no. 1, pp. 79–90, 1997.
[81]  M. G. Mytilinaiou and D. P. Bogdanos, “Primary biliary cirrhosis-specific autoantibodies in patients with systemic sclerosis,” Digestive and Liver Disease, vol. 41, no. 12, p. 916, 2009.
[82]  P. Invernizzi, C. Selmi, C. Ranftler, M. Podda, and J. Wesierska-Gadek, “Antinuclear antibodies in primary biliary cirrhosis,” Seminars in Liver Disease, vol. 25, no. 3, pp. 298–310, 2005.
[83]  D. P. Bogdanos, C. Liaskos, A. Pares et al., “Anti-gp210 antibody mirrors disease severity in primary biliary cirrhosis,” Hepatology, vol. 45, no. 6, p. 1583, 2007.
[84]  D. P. Bogdanos, C. Liaskos, E. I. Rigopoulou, and G. N. Dalekos, “Anti-mitochondrial antibodies in patients with systemic lupus erythematosus: revealing the unforeseen,” Clinica Chimica Acta, vol. 373, no. 1-2, pp. 183–184, 2006.
[85]  D. P. Bogdanos, A. Pares, J. Rodes, and D. Vergani, “Primary biliary cirrhosis specific antinuclear antibodies in patients from Spain,” The American Journal of Gastroenterology, vol. 99, no. 4, pp. 763–764, 2004.
[86]  P. Invernizzi, M. Podda, P. M. Battezzati et al., “Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis,” Journal of Hepatology, vol. 34, no. 3, pp. 366–372, 2001.
[87]  K. Miyachi, R. W. Hankins, H. Matsushima et al., “Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study,” Journal of Autoimmunity, vol. 20, no. 3, pp. 247–254, 2003.
[88]  M. Nakamura, H. Kondo, T. Mori et al., “Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis,” Hepatology, vol. 45, no. 1, pp. 118–127, 2007.
[89]  E. I. Rigopoulou, E. T. Davies, A. Pares et al., “Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis,” Gut, vol. 54, no. 4, pp. 528–532, 2005.
[90]  L. Dubel, A. Tanaka, P. S. C. Leung et al., “Autoepitope mapping and reactivity of autoantibodies to the dihydrolipoamide dehydrogenase-binding protein (E3BP) and the glycine cleavage proteins in primary biliary cirrhosis,” Hepatology, vol. 29, no. 4, pp. 1013–1018, 1999.
[91]  P. S. C. Leung, R. L. Coppel, A. Ansari, S. Munoz, and M. E. Gershwin, “Antimitochondrial antibodies in primary biliary cirrhosis,” Seminars in Liver Disease, vol. 17, no. 1, pp. 61–69, 1997.
[92]  J. M. Palmer, D. E. J. Jones, J. Quinn, A. McHugh, and S. J. Yeaman, “Characterization of the autoantibody responses to recombinant e3 binding protein (protein X) of pyruvate dehydrogenase in primary biliary cirrhosis,” Hepatology, vol. 30, no. 1, pp. 21–26, 1999.
[93]  J. Van de Water, D. Fregeau, P. Davis et al., “Autoantibodies of primary biliary cirrhosis recognize dihydrolipoamide acetyltransferase and inhibit enzyme function,” Journal of Immunology, vol. 141, no. 7, pp. 2321–2324, 1988.
[94]  S. Itoh, T. Ichida, T. Yoshida et al., “Autoantibodies against a 210 kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis,” Journal of Gastroenterology and Hepatology, vol. 13, no. 3, pp. 257–265, 1998.
[95]  K. Lassoued, M. N. Guilly, C. Andre et al., “Autoantibodies to 200 kd polypeptide(s) of the nuclear envelope: a new serologic marker of primary biliary cirrhosis,” Clinical and Experimental Immunology, vol. 74, no. 2, pp. 283–288, 1988.
[96]  P. Muratori, L. Muratori, R. Ferrari et al., “Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis,” American Journal of Gastroenterology, vol. 98, no. 2, pp. 431–437, 2003.
[97]  J. Wesierska-Gadek, E. Penner, P. M. Battezzati et al., “Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis,” Hepatology, vol. 43, no. 5, pp. 1135–1144, 2006.
[98]  W. H. Yang, J. H. Yu, A. Nakajima, D. Neuberg, K. Lindor, and D. B. Bloch, “Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure?” Clinical Gastroenterology and Hepatology, vol. 2, no. 12, pp. 1116–1122, 2004.
[99]  M. E. Gershwin, C. Selmi, H. J. Worman et al., “Risk factors and comorbidities in primary biliary cirrhosis: a controlled interview-based study of 1032 patients,” Hepatology, vol. 42, no. 5, pp. 1194–1202, 2005.
[100]  M. Hudson, A. Rojas-Villarraga, P. Coral-Alvarado et al., “Polyautoimmunity and familial autoimmunity in systemic sclerosis,” Journal of Autoimmunity, vol. 31, no. 2, pp. 156–159, 2008.
[101]  European Association for the Study of the Liver, “Easl clinical practice guidelines: management of cholestatic liver diseases,” Journal of Hepatology, vol. 51, no. 2, pp. 237–267, 2009.
[102]  R. Poupon, “Primary biliary cirrhosis: a 2010 update,” Journal of Hepatology, vol. 52, no. 5, pp. 745–758, 2010.
[103]  C. Corpechot, F. Carrat, R. Poupon, and R. Poupon, “Primary biliary cirrhosis: incidence and predictive factors of cirrhosis development in ursodiol-treated patients,” Gastroenterology, vol. 122, no. 3, pp. 652–658, 2002.
[104]  C. Selmi, F. Meda, A. Kasangian et al., “Experimental evidence on the immunopathogenesis of primary biliary cirrhosis,” Cellular and Molecular Immunology, vol. 7, no. 1, pp. 1–10, 2010.
[105]  M. E. Gershwin and I. R. Mackay, “The causes of primary biliary cirrhosis: convenient and inconvenient truths,” Hepatology, vol. 47, no. 2, pp. 737–745, 2008.
[106]  D. P. Bogdanos, H. Baum, D. Vergani, and A. K. Burroughs, “The role of E. coli infection in the pathogenesis of primary biliary cirrhosis,” Disease Markers, vol. 29, no. 6, pp. 301–311, 2010.
[107]  D. P. Bogdanos and D. Vergani, “Origin of cross-reactive autoimmunity in primary biliary cirrhosis,” Liver International, vol. 26, no. 6, pp. 633–635, 2006.
[108]  D. P. Bogdanos and D. Vergani, “Bacteria and primary biliary cirrhosis,” Clinical Reviews in Allergy and Immunology, vol. 36, no. 1, pp. 30–39, 2009.
[109]  M. E. Gershwin and I. R. Mackay, “Primary biliary cirrhosis: paradigm or paradox for autoimmunity,” Gastroenterology, vol. 100, no. 3, pp. 822–833, 1991.
[110]  D. E. J. Jones, “Enesis of primary biliary cirrhosis,” Gut, vol. 56, no. 11, pp. 1615–1624, 2007.
[111]  I. R. Mackay, S. Whittingham, S. Fida et al., “The peculiar autoimmunity of primary biliary cirrhosis,” Immunological Reviews, vol. 174, pp. 226–237, 2000.
[112]  S. Shimoda, M. Nakamura, H. Ishibashi, K. Hayashida, and Y. Niho, “Hla drb4 0101-restricted immunodominant t cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis: evidence of molecular mimicry in human autoimmune diseases,” Journal of Experimental Medicine, vol. 181, no. 5, pp. 1835–1845, 1995.
[113]  S. Shimoda, M. Nakamura, H. Shigematsu et al., “Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T-cell epitope of primary biliary cirrhosis,” Hepatology, vol. 31, no. 6, pp. 1212–1216, 2000.
[114]  S. Shimoda, J. Van De Water, A. Ansari et al., “Identification and precursor frequency analysis of a common t cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis,” Journal of Clinical Investigation, vol. 102, no. 10, pp. 1831–1840, 1998.
[115]  D. Smyk, E. Cholongitas, S. Kriese, E. I. Rigopoulou, and D. P. Bogdanos, “Primary biliary cirrhosis: family stories,” Autoimmune Diseases, vol. 2011, Article ID 189585, 11 pages, 2011.
[116]  D. S. Smyk, D. P. Bogdanos, S. Kriese, C. Billinis, A. K. Burroughs, and E. I. Rigopoulou, “Urinary tract infection as a risk factor for autoimmune liver disease: from bench to bedside,” Clinics and Research in Hepatology and Gastroenterology, vol. 36, no. 2, pp. 110–121, 2012.
[117]  D. S. Smyk, E. I. Rigopoulou, A. Lleo, et al., “Immunopathogenesis of Primary biliary cirrhosis: an old wives' tale,” Immunity & Ageing, vol. 8, no. 1, p. 12, 2011.
[118]  N. Agmon-Levin, B. S. Katz, and Y. Shoenfeld, “Infection and primary biliary cirrhosis,” The Israel Medical Association Journal, vol. 11, no. 2, pp. 112–115, 2009.
[119]  S. A. Morshed, M. Nishioka, I. Saito, K. Komiyama, and I. Moro, “Increased expression of Epstein-Barr virus in primary biliary cirrhosis patients,” Gastroenterologia Japonica, vol. 27, no. 6, pp. 751–758, 1992.
[120]  M. Lidar, P. Langevitz, O. Barzilai et al., “Infectious serologies and autoantibodies in inflammatory bowel disease: insinuations at a true pathogenic role,” Annals of the New York Academy of Sciences, vol. 1173, pp. 640–648, 2009.
[121]  H. Yanai, N. Shimizu, S. Nagasaki, N. Mitani, and K. Okita, “Epstein-Barr virus infection of the colon with inflammatory bowel disease,” American Journal of Gastroenterology, vol. 94, no. 6, pp. 1582–1586, 1999.
[122]  T. Akamatsu, N. Watanabe, and T. Chiba, “Epstein-Barr virus-associated lymphoma developed shortly after immunosuppressive treatment for ulcerative colitis,” Clinical Gastroenterology and Hepatology, vol. 5, no. 4, p. 521, 2007.
[123]  L. Origgi, C. Hu, E. Bertetti, et al., “Antibodies to Epstein-Barr virus and cytomegalovirus in primary Sjogren's syndrome,” Bollettino dell'Istituto Sieroterapico Milanese, vol. 67, no. 4, pp. 265–274, 1988.
[124]  K. Yamaoka, N. Miyasaka, and K. Yamamoto, “Possible involvement of Epstein-Barr virus in polyclonal b cell activation in sjogren's syndrome,” Arthritis and Rheumatism, vol. 31, no. 8, pp. 1014–1021, 1988.
[125]  P. V. Coyle, D. Wyatt, J. H. Connolly, and C. O'Brien, “Epstein-Barr virus infection and thyroid dysfunction,” Lancet, vol. 1, no. 8643, p. 899, 1989.
[126]  R. K. Pedersen and N. T. Pedersen, “Primary non-hodgkin's lymphoma of the thyroid gland: a population based study,” Histopathology, vol. 28, no. 1, pp. 25–32, 1996.
[127]  M. A. Alspaugh, G. Henle, E. T. Lennette, and W. Henle, “Elevated levels of antibodies to Epstein-Barr virus antigens in sera and synovial fluids of patients with rheumatoid arthritis,” Journal of Clinical Investigation, vol. 67, no. 4, pp. 1134–1140, 1981.
[128]  N. Balandraud, J. B. Meynard, I. Auger et al., “Epstein-Barr virus load in the peripheral blood of patients with rheumatoid arthritis: accurate quantification using real-time polymerase chain reaction,” Arthritis and Rheumatism, vol. 48, no. 5, pp. 1223–1228, 2003.
[129]  G. Niedobitek, R. Lisner, B. Swoboda, et al., “Lack of evidence for an involvement of Epstein-Barr virus infection of synovial membranes in the pathogenesis of rheumatoid arthritis,” Arthritis & Rheumatism, vol. 43, no. 1, pp. 151–154, 2000.
[130]  E. Scotet, M. A. Peyrat, X. Saulquin et al., “Frequent enrichment for cd8 t cells reactive against common herpes viruses in chronic inflammatory lesions: towards a reassessment of the physiopathological significance of t cell clonal expansions found in autoimmune inflammatory processes,” European Journal of Immunology, vol. 29, no. 3, pp. 973–985, 1999.
[131]  D. P. Bogdanos, H. Baum, A. Grasso et al., “Microbial mimics are major targets of crossreactivity with human pyruvate dehydrogenase in primary biliary cirrhosis,” Journal of Hepatology, vol. 40, no. 1, pp. 31–39, 2004.
[132]  D. P. Bogdanos, K. Choudhuri, and D. Vergani, “Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequences,” Liver, vol. 21, no. 4, pp. 225–232, 2001.
[133]  D. P. Bogdanos and L. Komorowski, “Disease-specific autoantibodies in primary biliary cirrhosis,” Clinica Chimica Acta, vol. 412, no. 7-8, pp. 502–512, 2011.
[134]  D. P. Bogdanos and E. I. Rigopoulou, “Self-mimicking autoimmune domains of hepatitis C virus core antigen,” Vaccine, vol. 24, no. 37–39, pp. 6173–6174, 2006.
[135]  D. P. Bogdanos, M. Okamoto, Y. Ma, R. Williams, G. Mieli-Vergani, and D. Vergani, “Virus/self double reactivity characterises the humoral immune response in autoimmune hepatitis-2,” Journal of Hepatology, vol. 32, article 45, 2000.
[136]  H. L. E. Lang, H. Jacobsen, S. Ikemizu et al., “A functional and structural basis for tcr cross-reactivity in multiple sclerosis,” Nature Immunology, vol. 3, no. 10, pp. 940–943, 2002.
[137]  M. R. Lerner, N. C. Andrews, G. Miller, and J. A. Steitz, “Two small rnas encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 78, no. 2, pp. 805–809, 1981.
[138]  A. Sabbatini, S. Bombardieri, and P. Migliorini, “Autoantibodies from patients with systemic lupus erythematosus bind a shared sequence of smd and Epstein-Barr virus-encoded nuclear antigen EBNA I,” European Journal of Immunology, vol. 23, no. 5, pp. 1146–1152, 1993.
[139]  K. W. Wucherpfennig and J. L. Strominger, “Molecular mimicry in t cell-mediated autoimmunity: viral peptides activate human t cell clones specific for myelin basic protein,” Cell, vol. 80, no. 5, pp. 695–705, 1995.
[140]  M. Massa, F. Mazzoli, P. Pignatti et al., “Proinflammatory responses to self hla epitopes are triggered by molecular mimicry to Epstein-Barr virus proteins in oligoarticular juvenile idiopathic arthritis,” Arthritis and Rheumatism, vol. 46, no. 10, pp. 2721–2729, 2002.
[141]  D. P. Bogdanos, M. Lenzi, M. Okamoto, et al., “Multiple viral/self immunological cross-reactivity in liver kidney microsomal antibody positive hepatitis C virus infected patients is associated with the possession of HLA B51,” International Journal of Immunopathology and Pharmacology, vol. 17, no. 1, pp. 83–92, 2004.
[142]  M. P. Manns, K. J. Griffin, K. F. Sullivan, and E. F. Johnson, “Lkm-1 autoantibodies recognize a short linear sequence in p450iid6, a cytochrome p-450 monooxygenase,” Journal of Clinical Investigation, vol. 88, no. 4, pp. 1370–1378, 1991.
[143]  D. Vergani and G. Mieli-Vergani, “Immunology of Autoimmune hepatitis,” Current Opinion in Gastroenterology, vol. 17, no. 6, pp. 562–567, 2001.
[144]  D. P. Bogdanos, Y. Ma, N. Hadzic, B. Portmann, G. Mieli-Vergani, and D. Vergani, “P0295 virus-self crossreactivity inducing De Novo autoimmune hepatitis eight-years after liver transplantation,” Journal of Pediatric Gastroenterology & Nutrition, vol. 39, p. S169, 2004.
[145]  D. P. Bogdanos, A. Pares, J. Rodes, and D. Vergani, “Primary biliary cirrhosis specific antinuclear antibodies in patients from Spain,” The American Journal of Gastroenterology, vol. 99, no. 4, pp. 763–764, 2004.
[146]  W. Xie and M. Snyder, “Two short autoepitopes on the nuclear dot antigen are similar to epitopes encoded by the Epstein-Barr virus,” Proceedings of the National Academy of Sciences of the United States of America, vol. 92, no. 5, pp. 1639–1643, 1995.
[147]  S. Vento, T. Garofano, G. Di Perri, L. Dolci, E. Concia, and D. Bassetti, “Identification of hepatitis a virus as a trigger for autoimmune chronic hepatitis type 1 in susceptible individuals,” Lancet, vol. 337, no. 8751, pp. 1183–1187, 1991.
[148]  S. Vento and F. Cainelli, “Is there a role for viruses in triggering autoimmune hepatitis?” Autoimmunity Reviews, vol. 3, no. 1, pp. 61–69, 2004.
[149]  S. Ferri, M. S. Longhi, C. De Molo et al., “A multifaceted imbalance of t cells with regulatory function characterizes type 1 autoimmune hepatitis,” Hepatology, vol. 52, no. 3, pp. 999–1007, 2010.
[150]  C. A. Aoki, C. M. Roifman, Z. X. Lian et al., “Il-2 receptor alpha deficiency and features of primary biliary cirrhosis,” Journal of Autoimmunity, vol. 27, no. 1, pp. 50–53, 2006.
[151]  K. Wakabayashi, Z. X. Lian, Y. Moritoki et al., “Il-2 receptor α(-/-) mice and the development of primary biliary cirrhosis,” Hepatology, vol. 44, no. 5, pp. 1240–1249, 2006.
[152]  R. Y. Lan, C. Cheng, Z. X. Lian et al., “Liver-targeted and peripheral blood alterations of regulatory t cells in primary biliary cirrhosis,” Hepatology, vol. 43, no. 4, pp. 729–737, 2006.
[153]  M. Tsuda, T. R. Torgerson, C. Selmi et al., “The spectrum of autoantibodies in ipex syndrome is broad and includes anti-mitochondrial autoantibodies,” Journal of Autoimmunity, vol. 35, no. 3, pp. 265–268, 2010.
[154]  K. G. Lucas, D. Ungar, M. Comito, and B. Groh, “Epstein barr virus induced lymphoma in a child with ipex syndrome,” Pediatric Blood and Cancer, vol. 50, no. 5, pp. 1056–1057, 2008.
[155]  M. P. Pender, “CD8+ T cell deficiency, Epstein-Barr virus infection, vitamin D deficiency and steps to autoimmunity: a unifying hypothesis,” Autoimmune Diseases, vol. 2012, Article ID 189096, 16 pages, 2012.

Full-Text

comments powered by Disqus