The immunopathogenetic role of autoantibodies in canine autoimmune hepatitis: lessons to learn from human autoimmune hepatitis
Tóm tắt
Autoimmune hepatitis (AIH) is not a disease entity restricted to man, but it can be found in other animals including canines. An increasing number of studies have focused on the immunopathogenesis of human autoimmune hepatitis (hAIH), but little is known of what triggers canine autoimmune hepatitis (cAIH). Several drugs, toxins, microbial and viral agents are able to induce autoantibodies and indeed immune-mediated chronic canine hepatitis with immunological and serological features similar of those seen in the human disease. We discuss the features of cAIH paying attention to the autoantibody profile of the disease in comparison to that seen in hAIH. We also discuss the immunomodulatory role of specific molecular signaling pathways such as those mediated by tumor growth factor and p38 mitogen-activated kinase in the induction of AIH, and the potential of these molecules to act as targets of specialized immunotherapeutic interventions. Review of the literature indicates that we have more to learn for the delineation of autoantibody profile and the antigen-specific immunoregulatory mechanisms involved in the pathogenesis of cAIH from the human disease, rather than the other way around.
Tài liệu tham khảo
Khanna C, Lindblad-Toh K, Vail D et al (2006) The dog as a cancer model. Nat Biotechnol 24:1065–1066
Favier RP, Spee B, Penning LC et al (2011) Copper-induced hepatitis: the COMMD1 deficient dog as a translational animal model for human chronic hepatitis. Vet Q 31:49–60
Debenham SL, Hart EA, Ashurst JL et al (2005) Genomic sequence of the class II region of the canine MHC: comparison with the MHC of other mammalian species. Genomics 85:48–59
Wilbe M, Jokinen P, Truve K et al (2010) Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex. Nat Genet 42:250–254
Lindblad-Toh K, Wade CM, Mikkelsen TS et al (2005) Genome sequence, comparative analysis and haplotype structure of the domestic dog. Nature 438:803–819
Rao NA, van Wolferen ME, van den Ham R et al (2008) cDNA microarray profiles of canine mammary tumour cell lines reveal deregulated pathways pertaining to their phenotype. Anim Genet 39:333–345
Sawhney R, Visvanathan K (2011) Polymorphisms of toll-like receptors and their pathways in viral hepatitis. Antivir Ther 16:443–458
Krawitt EL (2006) Autoimmune hepatitis. N Engl J Med 354:54–66
Watson PJ (2004) Chronic hepatitis in dogs: a review of current understanding of the aetiology, progression, and treatment. Vet J 167:228–241
Poldervaart JH, Favier RP, Penning LC et al (2009) Primary hepatitis in dogs: a retrospective review (2002–2006). J Vet Intern Med 23:72–80
Bexfield NH, Andres-Abdo C, Scase TJ et al (2011) Chronic hepatitis in the English springer spaniel: clinical presentation, histological description and outcome. Vet Rec 169:415
Shih JL, Keating JH, Freeman LM et al (2007) Chronic hepatitis in Labrador Retrievers: clinical presentation and prognostic factors. J Vet Intern Med 21:33–39
Crawford MA, Schall WD, Jensen RK et al (1985) Chronic active hepatitis in 26 Doberman pinschers. J Am Vet Med Assoc 187:1343–1350
Bishop L, Strandberg JD, Adams RJ et al (1979) Chronic active hepatitis in dogs associated with leptospires. Am J Vet Res 40:839–844
Jarrett WF, O’Neil BW (1985) A new transmissible agent causing acute hepatitis, chronic hepatitis and cirrhosis in dogs. Vet Rec 116:629–635
Rakich PM, Prasse KW, Lukert PD et al (1986) Immunohistochemical detection of canine adenovirus in paraffin sections of liver. Vet Pathol 23:478–484
Chouinard L, Martineau D, Forget C et al (1998) Use of polymerase chain reaction and immunohistochemistry for detection of canine adenovirus type 1 in formalin-fixed, paraffin-embedded liver of dogs with chronic hepatitis or cirrhosis. J Vet Diagn Invest 10:320–325
Kapoor A, Simmonds P, Gerold G et al (2011) Characterization of a canine homolog of hepatitis C virus. Proc Natl Acad Sci USA 108:11608–11613
Leifer CE, Page RL, Matus RE et al (1987) Proliferative glomerulonephritis and chronic active hepatitis with cirrhosis associated with Corynebacterium parvum immunotherapy in a dog. J Am Vet Med Assoc 190:78–80
Mylonakis ME, Kritsepi-Konstantinou M, Dumler JS et al (2010) Severe hepatitis associated with acute Ehrlichia canis infection in a dog. J Vet Intern Med 24:633–638
Rallis T, Day MJ, Saridomichelakis MN et al (2005) Chronic hepatitis associated with canine leishmaniosis (Leishmania infantum): a clinicopathological study of 26 cases. J Comp Pathol 132:145–152
Kearns S (2009) Infectious hepatopathies in dogs and cats. Top Companion Anim Med 24:189–198
Spee B, Arends B, van den Ingh TS et al (2006) Copper metabolism and oxidative stress in chronic inflammatory and cholestatic liver diseases in dogs. J Vet Intern Med 20:1085–1092
Sevelius E, Andersson M, Jonsson L (1994) Hepatic accumulation of alpha-1-antitrypsin in chronic liver disease in the dog. J Comp Pathol 111:401–412
Rogers WA, Ruebner BH (1977) A retrospective study of probable glucocorticoid-induced hepatopathy in dogs. J Am Vet Med Assoc 170:603–606
Bunch SE, Castleman WL, Hornbuckle WE et al (1982) Hepatic cirrhosis associated with long-term anticonvulsant drug therapy in dogs. J Am Vet Med Assoc 181:357–362
Gocke DJ, Morris TQ, Bradley SE (1970) Chronic hepatitis in the dog: the role of immune factors. J Am Vet Med Assoc 156:1700–1705
Mandigers PJ, van den Ingh TS, Spee B et al (2004) Chronic hepatitis in Doberman pinschers. A review. Vet Q 26:98–106
Sterczer A, Gaal T, Perge E et al (2001) Chronic hepatitis in the dog—a review. Vet Q 23:148–152
Strombeck DR, Gribble D (1978) Chronic active hepatitis in the dog. J Am Vet Med Assoc 173:380–386
Thornburg LP (1998) Histomorphological and immunohistochemical studies of chronic active hepatitis in Doberman Pinschers. Vet Pathol 35:380–385
Boisclair J, Dore M, Beauchamp G et al (2001) Characterization of the inflammatory infiltrate in canine chronic hepatitis. Vet Pathol 38:628–635
Fuentealba C, Guest S, Haywood S et al (1997) Chronic hepatitis: a retrospective study in 34 dogs. Can Vet J 38:365–373
Speeti M, Stahls A, Meri S et al (2003) Upregulation of major histocompatibility complex class II antigens in hepatocytes in Doberman hepatitis. Vet Immunol Immunopathol 96:1–12
Marcellin P (2009) Hepatitis B and hepatitis C in 2009. Liver Int 29(Suppl 1):1–8
Zignego AL, Piluso A, Giannini C (2008) HBV and HCV chronic infection: autoimmune manifestations and lymphoproliferation. Autoimmun Rev 8:107–111
Lai M, Liaw YF (2010) Chronic hepatitis B: past, present, and future. Clin Liver Dis 14:531–546
Shi YH, Shi CH (2009) Molecular characteristics and stages of chronic hepatitis B virus infection. World J Gastroenterol 15:3099–3105
Guidotti LG, Chisari FV (2006) Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol 1:23–61
Bogdanos DP, Mieli-Vergani G, Vergani D (2004) Non-organ-specific autoantibodies in children with chronic hepatitis C virus infection. Clin Infect Dis 38:1505 (author reply 1505–1506)
Bogdanos DP, Mieli-Vergani G, Vergani D (2005) Non-organ-specific autoantibodies in hepatitis C virus infection: do they matter? Clin Infect Dis 40:508–510
Obermayer-Straub P, Manns MP (2001) Hepatitis C and D, retroviruses and autoimmune manifestations. J Autoimmun 16:275–285
Bogdanos DP, Muratori L, Bianchi FB et al (2000) Hepatitis C virus and autoimmunity. Hepatology 31:1380
Gregorio GV, Choudhuri K, Ma Y et al (2003) 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 133:404–413
Bogdanos DP, Mieli-Vergani G, Vergani D (2009) Autoantibodies and their antigens in autoimmune hepatitis. Semin Liver Dis 29:241–253
Bogdanos DP, Dalekos GN (2008) Enzymes as target antigens of liver-specific autoimmunity: the case of cytochromes P450s. Curr Med Chem 15:2285–2292
Alvarez F, Berg PA, Bianchi FB et al (1999) International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 31:929–938
Hennes EM, Zeniya M, Czaja AJ et al (2008) Simplified criteria for the diagnosis of autoimmune hepatitis. Hepatology 48:169–176
Bogdanos DP, Invernizzi P, Mackay IR et al (2008) Autoimmune liver serology: current diagnostic and clinical challenges. World J Gastroenterol 14:3374–3387
Bogdanos DP, Mieli-Vergani G, Vergani D (2001) Liver-kidney microsomal antibody-positive autoimmune hepatitis in the United States. Am J Gastroenterol 96:3447–3448
Smith BE, Tompkins MB, Breitschwerdt EB (2004) Antinuclear antibodies can be detected in dog sera reactive to Bartonella vinsonii subsp. berkhoffii, Ehrlichia canis, or Leishmania infantum antigens. J Vet Intern Med 18:47–51
Kelly PJ, Carter SD, Bobade PA et al (1994) Absence of antinuclear antibodies in dogs infected with Ehrlichia canis. Vet Rec 134:382
Harrus S, Day MJ, Waner T et al (2001) Presence of immune-complexes, and absence of antinuclear antibodies, in sera of dogs naturally and experimentally infected with Ehrlichia canis. Vet Microbiol 83:343–349
Gershwin LJ (2005) Antinuclear antibodies in domestic animals. Ann N Y Acad Sci 1050:364–370
Saunders GK, Monroe WE (2006) Systemic granulomatous disease and sialometaplasia in a dog with Bartonella infection. Vet Pathol 43:391–392
Lenoir AA, Storch GA, DeSchryver-Kecskemeti K et al (1988) Granulomatous hepatitis associated with cat scratch disease. Lancet 1:1132–1136
Hopf U, Meyer zum Buschenfelde KH, Arnold W (1976) Detection of a liver-membrane autoantibody in HBsAg-negative chronic active hepatitis. N Engl J Med 294:578–582
Manns M, Meyer zum Buschenfelde KH, Hutteroth TH et al (1980) Detection and characterization of liver membrane autoantibodies in chronic active hepatitis by a solid-phase radioimmunoassay. Clin Exp Immunol 42:263–272
Meliconi R, Stancari MV, Garagnani M et al (1983) Occurrence and significance of IgG liver membrane autoantibodies (LMA) in chronic liver diseases of different aetiology. Clin Exp Immunol 51:565–571
Manns M, Meyer zum Buschenfelde KH, Hess G (1980) Autoantibodies against liver-specific membrane lipoprotein in acute and chronic liver diseases: studies on organ-, species-, and disease-specificity. Gut 21:955–961
Weiss DJ, Armstrong PJ, Mruthyunjaya A (1995) Anti-liver membrane protein antibodies in dogs with chronic hepatitis. J Vet Intern Med 9:267–271
Bogdanos DP, Bianchi I, Ma Y et al (2004) Targets of antibodies to soluble liver antigen in patients with autoimmune hepatitis. Clin Chem 50:682–683 (author reply 683–684)
Rigopoulou EI, Roggenbuck D, Smyk DS et al (2012) Asialoglycoprotein receptor (ASGPR) as target autoantigen in liver autoimmunity: lost and found. Autoimmun Rev
Bogdanos DP, Choudhuri K, Vergani D (2001) Molecular mimicry and autoimmune liver disease: virtuous intentions, malign consequences. Liver 21:225–232
Bogdanos DP, Lenzi M, Okamoto M et al (2004) 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. Int J Immunopathol Pharmacol 17:83–92
Bogdanos DP, McFarlane IG (2003) Cytochrome P450 2A6 meets P450 2D6: an enigma of viral infections and autoimmunity. J Hepatol 39:860–863
Bogdanos DP, Mieli-Vergani G, Vergani D (2000) Virus, liver and autoimmunity. Dig Liver Dis 32:440–446
Bogdanos DP, Rigopoulou EI (2006) Self-mimicking autoimmune domains of hepatitis C virus core antigen. Vaccine 24:6173–6174
Bogdanos DP, Rigopoulou EI (2007) Viral/self-mimicry and immunological cross-reactivity as a trigger of hepatic C virus associated autoimmune diabetes. Diabetes Res Clin Pract 77:155–156
Bogdanos DP, Smith H, Ma Y et al (2005) A study of molecular mimicry and immunological cross-reactivity between hepatitis B surface antigen and myelin mimics. Clin Dev Immunol 12:217–224
Muratori L, Bogdanos DP, Muratori P et al (2005) Susceptibility to thyroid disorders in hepatitis C. Clin Gastroenterol Hepatol 3:595–603
Kerkar N, Choudhuri K, Ma Y et al (2003) 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 170:1481–1489
Longhi MS, Hussain MJ, Bogdanos DP et al (2007) Cytochrome P450IID6-specific CD8 T cell immune responses mirror disease activity in autoimmune hepatitis type 2. Hepatology 46:472–484
Longhi MS, Ma Y, Bogdanos DP et al (2004) Impairment of CD4(+)CD25(+) regulatory T-cells in autoimmune liver disease. J Hepatol 41:31–37
Longhi MS, Ma Y, Mitry RR et al (2005) Effect of CD4+ CD25+ regulatory T-cells on CD8 T-cell function in patients with autoimmune hepatitis. J Autoimmun 25:63–71
Ma Y, Bogdanos DP, Hussain MJ et al (2006) Polyclonal T-cell responses to cytochrome P450IID6 are associated with disease activity in autoimmune hepatitis type 2. Gastroenterology 130:868–882
Bogdanos DP, Smyk DS, Rigopoulou EI et al (2012) Twin studies in autoimmune disease: genetics, gender and environment. J Autoimmun 38:J156–J169
Vergani D, Longhi MS, Bogdanos DP et al (2009) Autoimmune hepatitis. Semin Immunopathol 31:421–435
Bexfield NH, Buxton RJ, Vicek TJ et al (2012) Breed, age and gender distribution of dogs with chronic hepatitis in the United Kingdom. Vet J 193:124–128
