CONSIDERAÇOES SOBRE A PATOGENESE DA HEPATITE AUTO-IMUNE

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A busca de fatores de suscetibilidade genética é claramente importante devido à natureza auto-imune da doença. O fator mais importante já demonstrado é o gene HLA-DRB1, mas outros genes podem ter um papel no desencadeamento da doença.
gold9.jpg Autor:
Goldberg, anna carla
Columnista Experto de SIIC

Institución:
Hospital Português Salvador, Bahia, Brasil


Artículos publicados por Goldberg, anna carla
Coautores
Paulo Lisboa Bittencourt. Doutor em Gastroent*  Gilda Porta. Professora Livre Docente em Gast* 
*
Recepción del artículo
22 de Junio, 2004
Aprobación
16 de Septiembre, 2004
Primera edición
30 de Noviembre, 2004
Segunda edición, ampliada y corregida
7 de Junio, 2021

Resumen
A hepatite auto-imune (HAI) é uma doença inflamatória crônica do fígado que evolui para cirrose hepática, na ausência de tratamento imunossupressor. Bastante rara, pode acometer adultos e crianças. A base de sua classificação é a presença de auto-anticorpos circulantes, mas a doença é predominantemente causada por auto-imunidade celular. Em algumas formas da doença, os alvos antigênicos já puderam ser localizados, mas na maioria dos pacientes este é ainda desconhecido. A busca de fatores de suscetibilidade genética é claramente importante devido à natureza auto-imune da doença. O fator mais importante já demonstrado é o gene HLA-DRB1, mas outros genes podem ter um papel no desencadeamento da doença. A presença de certas variantes do gene HLA-DRB1 é um significante fator de risco. Alelos diferentes de HLA-DRB1, conforme a origem geográfica dos pacientes e de acordo com a forma clínica da doença, foram associados à HAI, indicando um quadro complexo e multifatorial onde participam outros fatores genéticos e ambientais ainda não conhecidos.

Palabras clave
Hepatite auto-imune, autoanticorpos, autoantígenos, susceptibilidade genética, antígenos HLA


Artículo completo

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Extensión:  +/-4.73 páginas impresas en papel A4
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Abstract
Autoimmune hepatitis is a chronic liver disease of unknown cause that leads, when untreated, to cirrhosis and liver failure. This rare disease affects adults and children and usually responds well to immunossupressive therapy. Autoimmune hepatitis is classified in two distinct types according to the autoantibody profile. Although the hallmark of the disease is the presence of autoantibodies in high titers, AIH is considered a cell mediated autoimmune disorder. Several antigens have been implicated in the disease pathogenesis, but in most patients, the target molecules involved remain to be established. Genetic susceptibility is clearly important due to the autoimmune nature of the disease. The major susceptibility factor identified up to now is the HLA-DRB1 locus but other genes may play a role in the development of the disease. Different alleles have been associated with the disease in different parts of the world. These findings altogether point to a complex interplay of MHC and non-MHC linked genetic factors and yet unknown environmental triggers in the pathogenesis of autoimmune hepatitis.

Key words
Autoimmune hepatitis, autoantibodies, autoantigens, genetic susceptibility, HLA antigens


Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
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Especialidades
Principal: Gastroenterología
Relacionadas: Infectología, Inmunología, Medicina Interna



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Goldberg, Anna Carla
Patrocinio y reconocimiento:
Parte dos trabalhos produzidos pelos autores foram financiados pelo CNPq.
Bibliografía del artículo
  1. Cançado ELR, Farias AQ, Bittencourt PL. Hepatite auto-imune. Em Silva LC. Hepatites agudas e crônicas. Sarvier, São Paulo, 2003: 278-295.
  2. Czaja AJ & Freese DK. Diagnosis and treatment of autoimmune hepatitis. AASLD Practice Guidelines. Hepatology 2002; 36: 479-497.
  3. Krawitt EL. Autoimmune hepatitis: Classification, heterogeneity, and treatment. Am. J. Med., 1994; 96:23S-6S.
  4. Hashimoto E, Lindor K, Homburger HA, et al. Immunohistochemical characterization of hepatic lymphocytes in primary biliary cirrhosis in comparison with primary sclerosing cholangitis and autoimmune chronic active hepatitis. Mayo Clin Proc 1993; 68:1049-55.
  5. Arenz M, Meyer zum Büschenfelde KW, Löhr HF. Limited T cell receptor Vβ-chain repertoire of liver-infiltrating T cells in autoimmune hepatitis. J Hepatol 1998; 28:70-7.
  6. Lohr HF, Pingel S, Weyer S, Fritz T, Galle PR. Individual and common antigen-recognition sites of liver-derived T cells in patients with autoimmune hepatitis. Scand J Immunol. 2003 57(4):384-90.
  7. Yoshizawa K, Ota M, Katsuyama Y, Ichijo T, Inada H, Umemura T, Tanaka E, Kiyosawa K. T cell repertoire in the liver of patients with autoimmune hepatitis. Hum Immunol. 1999;60(9):806-15.
  8. Gregorio GV, Portman B, Reid E et al. Autoimmune hepatitis in childhood – A 20-year experience. Hepatology 1997; 25:541-547.
  9. Paronetto F, Sagnelli E. Immunologic observations in chronic active hepatitis: a disease of different etiologies. Pathol Annu 1980; 10: 157-181.
  10. Mackay IR. Immunological aspects of chronic active hepatitis. Hepatology 1983; 3: 724-728.
  11. Silva LC, Carrilho FJ, Di Pietro A, et al. Chronic hepatitis in São Paulo, Brazil. General data and clinical forms. Gastrointest Hepatol 1986; 9: 340-343.
  12. Cançado ELR & Porta G. Autoimmune hepatitis in South America. Manns MP, Paumgartner G, Leuschner U, editors. In Immunology and the Liver. Falk symposium 114, Kluwer Academic Publishers and Falk Foundation, 2000, p. 82-92.
  13. Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999;31:929-38.
  14. Manns MP & Strassburg CP. Autoimmune hepatitis: Clinical Challenges. Gastroenterology 2001; 120: 1502-1517.
  15. Abuaf N, Johanet C, Homberg JC. Autoantibodies in autoimmune chronic active hepatitis. In: Krawitt E, Wiesner RH, ed. Autoimmune liver diseases. New York: Raven Press, 1991; 93-109.
  16. Czaja AJ. Autoimmune hepatitis. Evolving concepts and treatment strategies. Dig Dis Sci, 1995; 40:435-56.
  17. Obermayer-Straub P, Manns MP. Cytochromes P450 and UDP-glucuronosyl-transferases as hepatocellular autoantigens.Baillieres Clin Gastroenterol. 1996;10(3):501-32.
  18. Homberg JC, Abuaf N, Bernard O, et al. Chronic Active hepatitis associated with antiliver/kidney microsome antibody type 1: A second type of autoimmune hepatitis. Hepatology 1987;7:1333-9.
  19. Donaldson PT, Czaja AJ. Genetic effects on susceptibility, clinical expression, and treatment outcome of type 1 autoimmune hepatitis. Clin Liver Dis 2002; 6:419-37.
  20. Donaldson PT, Doherty DG, Hayllar KM et al. Susceptibility to autoimmune chronic active hepatitis: human leucocyte antigens DR4 and A1-B8-DR3 are independent risk factors. Hepatology 1991;13:701-706.
  21. Seki T, Kiyosawa K, Inoko H et al. Association of autoimmune hepatitis wiyh HLA-Bw54 and DR4 in Japanese patients. Hepatology 1990; 12:1300-1304.
  22. Qiu DK, Ma X. Relationship between human leukocyte antigen-DRB1 and autoimmune hepatitis type I in Chinese patients.J Gastroenterol Hepatol. 2003;18(1):63-7.
  23. Fainboim l, Marcos Y, Pando M et al. Chronic active autoimmune hepatitis in children. Strong association with a particular HLA-DR6 (DRB1* 1301) haplotype. Hum. Immunol. 1994;41:146-150
  24. Pando M, Larriba J, Fernandez GC, Fainboim H, Ciocca M, Ramonet M, et al. Pediatric and adult forms of type 1 autoimmune hepatitis in Argentina: evidence for differential genetic predisposition. Hepatology 1999;30:1374-1380.
  25. Vazquez-Garcia MN, Alaez C, Olivo A, Debaz H, Perez-Luque E, Burguete A, et al. MHC class II sequences of susceptibility and protection in Mexicans with autoimmune hepatitis. J Hepatol. 1998;28:985-990.
  26. Bittencourt PL, Goldberg AC, Cançado ER, Porta G et al. Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2. Am. J. Gastroenterol. 1999; 94: 1906-1913.
  27. Bittencourt PL, Goldberg AC, Cançado ELR, Porta G, Laudanna AA, Kalil, J. Different HLA profiles confer susceptibility to Autoimmune Hepatitis Type 1 and 2. Letter to the Editor. Amer J Gastroent 1998; 93 (8): 1394-1395.
  28. Goldberg AC, Bittencourt PL, Mougin B, Cançado ELR, Porta G, Carrilho F, Kalil J. Analysis of HLA haplotypes in autoimmune hepatitis type 1: identifying the major susceptibility locus, Human Immunol 2001; 62(2): 165-9.
  29. Czaja AJ, Strettell MDJ, Thomson LJ, et al. Associations between alleles of the major histocompatibility complex and type 1 autoimmune hepatitis. Hepatology 1997;25:317-323.
  30. Strettell MDJ, Donaldson PT, Thomson LJ, SB, et al. Allelic basis for HLA-encoded susceptibility to type 1 autoimmune hepatitis. Gastroenterology 1997;112:2028-2035.
  31. Doherty DG, Donaldson PT, Underhill JA, Farrant JM, Duthie A, Mieli-Vergani G, et al. Allelic sequence variation in the HLA class II genes and proteins in patients with autoimmune hepatitis. Hepatology 1994;19:609-615.
  32. Seki T, Ota M, Furuta S, Fukushima H, Kondo T, Hino K, et al. HLA class II molecules and autoimmune hepatitis susceptibility in Japanese patients. Gastroenterology 1992;103:1041-1047.
  33. Czaja AJ, Souto EO, Bittencourt PL, et al. Clinical distinctions and pathogenetic implications of type 1 autoimmune hepatitis in Brazil and the United States. J Hepatol 2002; 37: 302-308.
  34. Yamamoto AM, Cresteil D, Boniface O et al. Identification and analysis of cytochrome P450IID6 antigenic sites recognized by anti-liver-kidney microsome type-1 antibodies (KLM-1). Eur. J. Immunol 1993; 23:1105-1111.
  35. Manns MP, Johnson EF, Griffin KJ et al. Major antigen of liver kidney microsomal antibodies in idiopathic autoimmune hepatitis is cytochrome P450db1. J. Clin. Invest. 1989; 83:1066-1072.
  36. Sugimura T, Obermayer-Straub P, Kayser A, Braun S, Loges S, Alex B, Luttig B, Johnson EF, Manns MP, Strassburg CP. A major CYP2D6 autoepitope in autoimmune hepatitis type 2 and chronic hepatitis C is a three-dimensional structure homologous to other cytochrome P450 autoantigens. Autoimmunity 2002;35(8):501-13.
  37. Czaja AJ, Shums Z, Norman GL. Frequency and significance of antibodies to soluble liver antigen/liver pancreas in variant autoimmune hepatitis.Autoimmunity 2002 ;35(8):475-83.
  38. Murota M, Watanabe S, Fujita J, Ohtsuki Y, Wu F, Yoshida S, Kita Y, Funakoshi F, Masaki T, Kurokohchi K, Uchida N, Ishida T, Kuriyama S. Aberrant cytokeratin expression and high susceptibility to apoptosis in autoimmune hepatitis. Hepatol Res. 2003;25(3):271-280.
  39. Miyakawa H, Kawashima Y, Kitazawa E, Kawaguchi N, Kato T, Kikuchi K, Imai E, Fujikawa H, Hashimoto E, Schlumberger W. Low frequency of anti-SLA/LP autoantibody in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay. J Autoimmun. 2003;21(1):77-82.
  40. Lapierre P, Johanet C, Alvarez F. Characterization of the B cell response of patients with anti-liver cytosol autoantibodies in type 2 autoimmune hepatitis.Eur J Immunol. 2003;33(7):1869-78.
  41. Kato T, Miyakawa H, Ishibashi M. Frequency and significance of anti-glutathione S-transferase autoantibody (anti-GST A1-1) in autoimmune hepatitis. J Autoimmun. 2004;22(3):211-6.
  42. Zamanou A, Samiotaki M, Panayotou G, Margaritis L, Lymberi P. Fine specificity and subclasses of IgG anti-actin autoantibodies differ in health and disease. J Autoimmun. 2003;20(4):333-44.
  43. Manns MP. Hepatotropic viruses and autoimmunity 1997. J Viral Hepatitis 1997;4:1-7
  44. Vento S, Garofano T, Di Perri G, Dolci L, Concia E, Bassetti D. Identification of hepatitis A virus as a trigger for autoimmune chronic hepatitis type 1 in susceptible individuals. Lancet 1991;337:1183-1187.
  45. Fainboim L, Velasco VCC, Marcos CY, Ciocca M, Roy A, Theiler G et al. Protracted, but not acute, hepatitis A virus infection is strongly associated with HLA-DRB1*1301, a marker for pediatric autoimmune hepatitis. Hepatology 2001;33:1512-1517.
  46. Gabbiani G, Ryan GB, Lamelin JP, Vassali P, Majno G, Bouvier CA et al. Human smooth muscle auto-antibody. Its identification as antiactin antibody and a study of its binding to "non muscular" cells. Am J Pathol 1973; 72: 473-88.
  47. Morshed SA, Parveen S, Nishioka M. Antibodies to cytoskeleton antigens in autoimmune liver diseases. In: Krawitt EL, Wiesner RH, Nishioka M ed. Autoimmune liver diseases. New York, Elsevier Science BV, 1998; p.217-256.
  48. Cançado ER, Vilas-Boas LS, Abrantes-Lemos CP et al. Heat serum inactivation as a mandatory procedure for anti-actin antibody detection in cell culture. Hepatology 1996, 23:1098-1104.
  49. Cookson S, Constantini PK, Clare M, Underhill JA, Bernal W, Czaja AJ et al. Frequency and nature of cytokine gene polymorphisms in type 1 autoimmune hepatitis. Hepatology 1999;30:851-856.
  50. Czaja AJ, Cookson S, Constantini PK, Clare M, Underhill JA, Donaldson PT. Cytokine polymorphisms associated with clinical features and treatment outcome in type 1 autoimmune hepatitis. Gastroenterology 1999;117:645-652.
  51. Bittencourt PL, Palacios SA, Cancado ELR, Porta G, Drigo S, Carrilho FJ et al. Autoimmune hepatitis in Brazilian patients is not linked to tumor necrosis factor polymorphisms at position -308. J Hepatol 2001;35:24-28.
  52. Agarwal K, Czaja AJ, Jones DEJ et al. CTLA-4 gene polymorphism and susceptibility to type 1 autoimmune hepatitis. Hepatology 2000;31:49-53.
  53. Bittencourt PL, Palacios SA, Cancado EL, Porta G, Carrilho FJ, Laudanna AA, Kalil J, Goldberg AC. Cytotoxic T lymphocyte antigen-4 gene polymorphisms do not confer susceptibility to autoimmune hepatitis types 1 and 2 in Brazil. Am J Gastroenterol. 2003;98(7):1616-20.

 
 
 
 
 
 
 
 
 
 
 
 
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