Pathogenesis of autoimmune hepatitis

Best Practice and Research: Clinical Gastroenterology

Volumn 25, Issue 6, 2011, Pages 653-664

  Liberal, Rodrigo ^a,b   Longhi, Maria Serena ^a   Mieli Vergani, Giorgina ^a   Vergani, Diego ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b University of Porto   (Portugal)

Author keywords

Cellular immunity; Humoural immunity; Immune regulation; Liver

Indexed keywords

AUTOANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; GAMMA INTERFERON; HLA DR ANTIGEN; INTERLEUKIN 1; INTERLEUKIN 10; INTERLEUKIN 13; INTERLEUKIN 2; INTERLEUKIN 4; INTERLEUKIN 6; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA;

ANTIGEN RECOGNITION; ARTICLE; AUTOIMMUNE HEPATITIS; AUTOIMMUNE POLYENDOCRINOPATHY CANDIDIASIS ECTODERMAL DYSTROPHY; AUTOIMMUNITY; CD4+ CD25+ T LYMPHOCYTE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELLULAR IMMUNITY; CYTOKINE PRODUCTION; GENE MUTATION; GENETIC PREDISPOSITION; HEREDITY; HISTOPATHOLOGY; HUMAN; HUMORAL IMMUNITY; IMMUNOPATHOGENESIS; INFLAMMATORY INFILTRATE; LIVER INJURY; MOLECULAR MIMICRY; MONOCYTE; NONHUMAN; REGULATORY T LYMPHOCYTE; TH1 CELL; TH17 CELL; TH2 CELL;

ANIMALS; DISEASE MODELS, ANIMAL; HEPATITIS, AUTOIMMUNE; HUMANS; IMMUNITY, CELLULAR; IMMUNITY, HUMORAL; MICE; T-LYMPHOCYTES, HELPER-INDUCER; T-LYMPHOCYTES, REGULATORY;

EID: 82255191476     PISSN: 15216918     EISSN: 15321916     Source Type: Journal    
DOI: 10.1016/j.bpg.2011.09.009     Document Type: Article

References (78)

1. P.T. Donaldson Genetics of liver disease: immunogenetics and disease pathogenesis Gut 53 2004 599 608 (Pubitemid 38372988)
2. P.T. Donaldson Genetics in autoimmune hepatitis Semin Liver Dis 22 2002 353 364
3. D. Vergani, K. Choudhuri, D.P. Bogdanos, and G. Mieli-Vergani Pathogenesis of autoimmune hepatitis Clin Liver Dis 6 2002 727 737
4. P.T. Donaldson, D.G. Doherty, K.M. Hayllar, I.G. McFarlane, P.J. Johnson, and R. Williams Susceptibility to autoimmune chronic active hepatitis: human leukocyte antigens DR4 and A1-B8-DR3 are independent risk factors Hepatology 13 1991 701 706
5. M.D. Strettell, P.T. Donaldson, and L.J. Thomson Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis Gastroenterology 112 1997 2028 2035 (Pubitemid 27240790)
6. P.T. Donaldson Genetics of autoimmune and viral liver diseases; understanding the issues J Hepatol 41 2004 327 332 (Pubitemid 39177639)
7. A.J. Czaja, and P.T. Donaldson Genetic susceptibilities for immune expression and liver cell injury in autoimmune hepatitis Immunol Rev 174 2000 250 259 (Pubitemid 30201393)
8. A.J. Czaja, D.G. Doherty, and P.T. Donaldson Genetic bases of autoimmune hepatitis Dig Dis Sci 47 2002 2139 2150 (Pubitemid 35205286)
9. D. Vergani, M.S. Longhi, D.P. Bogdanos, Y. Ma, and G. Mieli-Vergani Autoimmune hepatitis Semin Immunopathol 31 2009 421 435
10. C. Duarte-Rey, A.L. Pardo, Y. Rodriguez-Velosa, R.D. Mantilla, J.M. Anaya, and A. Rojas-Villarraga HLA class II association with autoimmune hepatitis in Latin America: a meta-analysis Autoimmun Rev 8 2009 325 331
11. Y. Ma, D.P. Bogdanos, and M.J. Hussain Polyclonal T-cell responses to cytochrome P450IID6 are associated with disease activity in autoimmune hepatitis type 2 Gastroenterology 130 2006 868 882 (Pubitemid 43374534)
12. I. Djilali-Saiah, R. Renous, S. Caillat-Zucman, D. Debray, and F. Alvarez Linkage disequilibrium between HLA class II region and autoimmune hepatitis in pediatric patients J Hepatol 40 2004 904 909 (Pubitemid 38670123)
13. I. Djilali-Saiah, A. Fakhfakh, H. Louafi, S. Caillat-Zucman, D. Debray, and F. Alvarez HLA class II influences humoral autoimmunity in patients with type 2 autoimmune hepatitis J Hepatol 45 2006 844 850 (Pubitemid 44646681)
14. G.V. Gregorio, B. Portmann, and F. Reid Autoimmune hepatitis in childhood: a 20-year experience Hepatology 25 1997 541 547 (Pubitemid 27106430)
15. I. Vorechovsky, A.D. Webster, A. Plebani, and L. Hammarstrom Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences, and the role of anti-IgA antibodies in disease predisposition Am J Hum Genet 64 1999 1096 1109 (Pubitemid 30463041)
16. D. Vergani, L. Wells, and V.F. Larcher Genetically determined low C4: a predisposing factor to autoimmune chronic active hepatitis Lancet 2 1985 294 298 (Pubitemid 15045129)
17. K. Agarwal, A.J. Czaja, D.E. Jones, and P.T. Donaldson Cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms and susceptibility to type 1 autoimmune hepatitis Hepatology 31 2000 49 53 (Pubitemid 30033688)
18. D. Vergani, and G. Mieli-Vergani Aetiopathogenesis of autoimmune hepatitis World J Gastroenterol 14 2008 3306 3312
19. A.J. Czaja, S. Cookson, P.K. Constantini, M. Clare, J.A. Underhill, and P.T. Donaldson Cytokine polymorphisms associated with clinical features and treatment outcome in type 1 autoimmune hepatitis Gastroenterology 117 1999 645 652 (Pubitemid 29409251)
20. K. Yoshizawa, M. Ota, and Y. Katsuyama Genetic analysis of the HLA region of Japanese patients with type 1 autoimmune hepatitis J Hepatol 42 2005 578 584 (Pubitemid 40342939)
21. K. Agarwal, A.J. Czaja, and P.T. Donaldson A functional Fas promoter polymorphism is associated with a severe phenotype in type 1 autoimmune hepatitis characterized by early development of cirrhosis Tissue Antigens 69 2007 227 235 (Pubitemid 46696944)
22. A. Vogel, C.P. Strassburg, and M.P. Manns Genetic association of vitamin D receptor polymorphisms with primary biliary cirrhosis and autoimmune hepatitis Hepatology 35 2002 126 131 (Pubitemid 34032552)
23. D. Mathis, and C. Benoist Aire Annu Rev Immunol 27 2009 287 312
24. M.J. Simmonds, and S.C. Gough Genetic insights into disease mechanisms of autoimmunity Br Med Bull 71 2004 93 113 (Pubitemid 40478224)
25. A. Liston, D.H. Gray, and S. Lesage Gene dosage-limiting role of Aire in thymic expression, clonal deletion, and organ-specific autoimmunity J Exp Med 200 2004 1015 1026 (Pubitemid 39431126)
26. A. Liston, S. Lesage, D.H. Gray, R.L. Boyd, and C.C. Goodnow Genetic lesions in T-cell tolerance and thresholds for autoimmunity Immunol Rev 204 2005 87 101 (Pubitemid 40460495)
27. M.S. Longhi, Y. Ma, G. Mieli-Vergani, and D. Vergani Aetiopathogenesis of autoimmune hepatitis J Autoimmun 34 2010 7 14
28. V. Racanelli, and B. Rehermann The liver as an immunological organ Hepatology 43 2006 S54 S62
29. I.R. Mackay Hepatoimmunology: a perspective Immunol Cell Biol 80 2002 36 44
30. I.N. Crispe The liver as a lymphoid organ Annu Rev Immunol 27 2009 147 163
31. K.T. Nouri-Aria, J.E. Hegarty, G.J. Alexander, A.L. Eddleston, and R. Williams Effect of corticosteroids on suppressor-cell activity in "autoimmune" and viral chronic active hepatitis N Engl J Med 307 1982 1301 1304 (Pubitemid 12005664)
32. H.J. Hodgson, J.R. Wands, and K.J. Isselbacher Alteration in suppressor cell activity in chronic active hepatitis Proc Natl Acad Sci U S A 75 1978 1549 1553 (Pubitemid 8301596)
33. S. Vento, J.E. Hegarty, G. Bottazzo, E. Macchia, R. Williams, and A.L. Eddleston Antigen specific suppressor cell function in autoimmune chronic active hepatitis Lancet 1 1984 1200 1204 (Pubitemid 14105853)
34. 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 J Hepatol 41 2004 31 37 (Pubitemid 39005149)
35. M.S. Longhi, Y. Ma, and R.R. Mitry Effect of CD4 + CD25 + regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis J Autoimmun 25 2005 63 71 (Pubitemid 41008667)
36. M.S. Longhi, M.J. Hussain, and R.R. Mitry Functional study of CD4 + CD25+regulatory T-cells in health and autoimmune hepatitis J Immunol 176 2006 4484 4491 (Pubitemid 44264429)
37. M.S. Longhi, F. Meda, and P. Wang Expansion and de novo generation of potentially therapeutic regulatory T-cells in patients with autoimmune hepatitis Hepatology 47 2008 581 591 (Pubitemid 351280726)
38. S. Ferri, M.S. Longhi, and C. De Molo A multifaceted imbalance of T-cells with regulatory function characterizes type 1 autoimmune hepatitis Hepatology 52 2010 999 1007
39. M.S. Longhi, M.J. Hussain, W.W. Kwok, G. Mieli-Vergani, Y. Ma, and D. Vergani Autoantigen-specific regulatory T-cells, a potential tool for immune-tolerance reconstitution in type-2 autoimmune hepatitis Hepatology 53 2011 536 547
40. S. Sakaguchi, M. Miyara, C.M. Costantino, and D.A. Hafler FOXP3 + regulatory T cells in the human immune system Nat Rev Immunol 10 2010 490 500
41. D.A. Vignali, L.W. Collison, and C.J. Workman How regulatory T cells work Nat Rev Immunol 8 2008 523 532
42. P.C. Janson, M.E. Winerdal, P. Marits, M. Thorn, R. Ohlsson, and O. Winqvist FOXP3 promoter demethylation reveals the committed Treg population in humans PLoS One 3 2008 e1612
43. A.M. Thornton, P.E. Korty, and D.Q. Tran Expression of Helios, an Ikaros transcription factor family member, differentiates thymic-derived from peripherally induced Foxp3 + T regulatory cells J Immunol 184 2010 3433 3441
44. M.S. Longhi, R.R. Mitry, and M. Samyn Vigorous activation of monocytes in juvenile autoimmune liver disease escapes the control of regulatory T-cells Hepatology 50 2009 130 142
45. J.L. Riley, C.H. June, and B.R. Blazar Human T regulatory cell therapy: take a billion or so and call me in the morning Immunity 30 2009 656 665
46. A.N. Akbar, L.S. Taams, M. Salmon, and M. Vukmanovic-Stejic The peripheral generation of CD4 + CD25 + regulatory T cells Immunology 109 2003 319 325 (Pubitemid 36783254)
47. M.S. Longhi, R. Liberal, G. Mieli-Vergani, Y. Ma, and D. Vergani Inhibition of Th17-cells enhances the suppressor function of de novo generated T-Reg in patients with autoimmune hepatitis Hepatology 50 2011 1012a-a
48. E. Bettelli, Y. Carrier, and W. Gao Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells Nature 441 2006 235 238
49. M. Gueguen, M. Meunier-Rotival, O. Bernard, and F. Alvarez Anti-liver-kidney-microsome-antibody recognizes a cytochrome P450 from the IID subfamily J Exp Med 168 1988 801 806
50. N. Kerkar, K. Choudhuri, and Y. Ma Cytochrome P4502D6(193-212): a new immunodominant epitope and target of virus/self cross-reactivity in liver kidney microsomal autoantibody type 1-positive liver disease J Immunol 170 2003 1481 1489 (Pubitemid 36139518)
51. M.S. Longhi, M.J. Hussain, and D.P. Bogdanos Cytochrome P450IID6-specific CD8 T-cell immune responses mirror disease activity in autoimmune hepatitis type 2 Hepatology 46 2007 472 484 (Pubitemid 47344783)
52. T. Santodomingo-Garzon, and M.G. Swain Role of NKT cells in autoimmune liver disease Autoimmun Rev 2011
53. D.P. Bogdanos, K. Choudhuri, and D. Vergani Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequences Liver 21 2001 225 232 (Pubitemid 32677377)
54. G.V. Gregorio, K. Choudhuri, Y. Ma, A. Vegnente, G. Mieli-Vergani, and D. Vergani Mimicry between the hepatitis B virus DNA polymerase and the antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis B virus infection J Immunol 162 1999 1802 1810 (Pubitemid 29307061)
55. G.V. Gregorio, K. Choudhuri, and Y. Ma Mimicry between the hepatitis C virus polyprotein and antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis C virus infection Clin Exp Immunol 133 2003 404 413 (Pubitemid 37046966)
56. M. Lenzi, S. Bellentani, and G. Saccoccio Prevalence of non-organ-specific autoantibodies and chronic liver disease in the general population: a nested case-control study of the Dionysos cohort Gut 45 1999 435 441 (Pubitemid 29400723)
57. 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 J Clin Invest 88 1991 1370 1378
58. G. Senaldi, B. Portmann, A.P. Mowat, G. Mieli-Vergani, and D. Vergani Immunohistochemical features of the portal tract mononuclear cell infiltrate in chronic aggressive hepatitis Arch Dis Child 67 1992 1447 1453 (Pubitemid 23008268)
59. A. Lobo-Yeo, G. Senaldi, B. Portmann, A.P. Mowat, G. Mieli-Vergani, and D. Vergani Class I and class II major histocompatibility complex antigen expression on hepatocytes: a study in children with liver disease Hepatology 12 1990 224 232 (Pubitemid 20285784)
60. G. Senaldi, A. Lobo-Yeo, A.P. Mowat, G. Mieli-Vergani, and D. Vergani Class I and class II major histocompatibility complex antigens on hepatocytes: importance of the method of detection and expression in histologically normal and diseased livers J Clin Pathol 44 1991 107 114
61. P. Miossec, T. Korn, and V.K. Kuchroo Interleukin-17 and type 17 helper T cells N Engl J Med 361 2009 888 898
62. T. Korn, E. Bettelli, M. Oukka, and V.K. Kuchroo IL-17 and Th17 cells Annu Rev Immunol 27 2009 485 517
63. K. Harada, S. Shimoda, Y. Sato, K. Isse, H. Ikeda, and Y. Nakanuma Periductal interleukin-17 production in association with biliary innate immunity contributes to the pathogenesis of cholangiopathy in primary biliary cirrhosis Clin Exp Immunol 157 2009 261 270
64. L. Zhao, Y. Tang, and Z. You Interleukin-17 contributes to the pathogenesis of autoimmune hepatitis through inducing hepatic interleukin-6 expression PLoS One 6 2011 e18909
65. D.M. Jensen, I.G. McFarlane, B.S. Portmann, A.L. Eddleston, and R. Williams Detection of antibodies directed against a liver-specific membrane lipoprotein in patients with acute and chronic active hepatitis N Engl J Med 299 1978 1 7 (Pubitemid 8387363)
66. B.M. McFarlane, C.G. McSorley, D. Vergani, I.G. McFarlane, and R. Williams Serum autoantibodies reacting with the hepatic asialoglycoprotein receptor protein (hepatic lectin) in acute and chronic liver disorders J Hepatol 3 1986 196 205 (Pubitemid 17173105)
67. G.M. Vergani, D. Vergani, and P.J. Jenkins Lymphocyte cytotoxicity to autologous hepatocytes in HBsAg-negative chronic active hepatitis Clin Exp Immunol 38 1979 16 21 (Pubitemid 9242141)
68. D. Vergani, G. Mieli-Vergani, M. Mondelli, B. Portmann, and A.L. Eddleston Immunoglobulin on the surface of isolated hepatocytes is associated with antibody-dependent cell-mediated cytotoxicity and liver damage Liver 7 1987 307 315 (Pubitemid 18013807)
69. Y. Ma, M. Okamoto, and M.G. Thomas Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease Hepatology 35 2002 658 664 (Pubitemid 34183971)
70. L. Muratori, M. Parola, A. Ripalti, G. Robino, P. Muratori, and G. Bellomo Liver/kidney microsomal antibody type 1 targets CYP2D6 on hepatocyte plasma membrane Gut 46 2000 553 561 (Pubitemid 30305822)
71. Y. Ma, M.G. Thomas, and M. Okamoto Key residues of a major cytochrome P4502D6 epitope are located on the surface of the molecule J Immunol 169 2002 277 285 (Pubitemid 34686146)
72. L. Wen, M. Peakman, and A. Lobo-Yeo T-cell-directed hepatocyte damage in autoimmune chronic active hepatitis Lancet 336 1990 1527 1530
73. L. Wen, Y. Ma, and D.P. Bogdanos Pediatric autoimmune liver diseases: the molecular basis of humoral and cellular immunity Curr Mol Med 1 2001 379 389 (Pubitemid 33772964)
74. H. Lohr, M. Manns, and A. Kyriatsoulis Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibody-positive autoimmune chronic active hepatitis Clin Exp Immunol 84 1991 297 302
75. T. Kreslavsky, M. Gleimer, A.I. Garbe, and H. von Boehmer alphabeta versus gammadelta fate choice: counting the T-cell lineages at the branch point Immunol Rev 238 2010 169 181
76. L. Wen, M. Peakman, G. Mieli-Vergani, and D. Vergani Elevation of activated gamma delta T cell receptor bearing T lymphocytes in patients with autoimmune chronic liver disease Clin Exp Immunol 89 1992 78 82
77. P. Lapierre, I. Djilali-Saiah, S. Vitozzi, and F. Alvarez A murine model of type 2 autoimmune hepatitis: Xenoimmunization with human antigens Hepatology 39 2004 1066 1074 (Pubitemid 38428946)
78. M. Holdener, E. Hintermann, M. Bayer, A. Rhode, E. Rodrigo, and G. Hintereder Breaking tolerance to the natural human liver autoantigen cytochrome P450 2D6 by virus infection J Exp Med 205 2008 1409 1422 (Pubitemid 351831496)