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Autoantibodies in Primary Biliary Cirrhosis

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Autoimmune Liver Diseases

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Abstract

Autoantibodies directed against a variety of mitochondrial antigens are a serological hallmark of primary biliary cirrhosis (PBC). Even with progress in the development of accurate and sensitive solid-phase assays for the detection of antimitochondrial antibody (AMA), a small but substantial number of patients are still regarded as having AMA-negative PBC. PBC-specific antinuclear antibodies (ANAs) are thus valuable as complementary serological markers for the definite diagnosis of AMA-negative PBC. Specific ANAs, particularly against proteins in the nuclear envelope, e.g., anti-gp210 antibody, possess additional and unexpected clinical significance in the prediction of PBC outcomes and possibly in disease activity; positivity for anti-gp210 antibody at the initial diagnosis is an independent predictive factor for poor prognosis and may influence the mode of disease progress. The combined use of particular ANAs in conjunction with an AMA should be advantageous for accurate and precise diagnoses and even for disease outcomes. The PBC landscape has been steadily changing with the progress in autoantibody research.

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References

  1. Lindor KD, Gershwin ME, Poupon R et al (2009) Primary biliary cirrhosis. Hepatology 50(1):291–308. doi:10.1002/hep.22906

    Article  PubMed  Google Scholar 

  2. European Association for the Study of the Liver (2009) EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol 51(2):237–267. doi:10.1016/j.jhep.2009.04.009

    Article  Google Scholar 

  3. Invernizzi P, Crosignani A, Battezzati PM et al (1997) Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and -negative primary biliary cirrhosis. Hepatology 25(5):1090–1095

    Article  CAS  PubMed  Google Scholar 

  4. Gershwin ME, Mackay IR, Sturgess A et al (1987) Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis. J Immunol 138(10):3525–3531

    CAS  PubMed  Google Scholar 

  5. Bogdanos DP, Komorowski L (2011) Disease-specific autoantibodies in primary biliary cirrhosis. Clin Chim Acta 412(7–8):502–512. doi:10.1016/j.cca.2010.12.019

    Article  CAS  PubMed  Google Scholar 

  6. Nakamura M, Kondo H, Mori T et al (2007) Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis. Hepatology 45(1):118–127

    Article  CAS  PubMed  Google Scholar 

  7. Hirschfield GM, Gershwin ME (2013) The immunobiology and pathophysiology of primary biliary cirrhosis. Annu Rev Pathol 8:303–330. doi:10.1146/annurev-pathol-020712-164014

    Article  CAS  PubMed  Google Scholar 

  8. Miyakawa H, Tanaka A, Kikuchi K et al (2001) Detection of antimitochondrial autoantibodies in immunofluorescent AMA-negative patients with primary biliary cirrhosis using recombinant autoantigens. Hepatology 34(2):243–248. doi:10.1053/jhep.2001.26514

    Article  CAS  PubMed  Google Scholar 

  9. Oertelt S, Rieger R, Selmi C et al (2007) A sensitive bead assay for antimitochondrial antibodies: chipping away at AMA-negative primary biliary cirrhosis. Hepatology 45(3):659–665. doi:10.1002/hep.21583

    Article  CAS  PubMed  Google Scholar 

  10. Shimoda S, Nakamura M, Ishibashi H et al (1995) HLA DRB4 0101-restricted immunodominant T cell autoepitope of pyruvate dehydrogenase complex in primary biliary cirrhosis—evidence of molecular mimicry in human autoimmune diseases. J Exp Med 181(5):1835–1845

    Article  CAS  PubMed  Google Scholar 

  11. Kamihira T, Shimoda S, Harada K et al (2003) Distinct costimulation dependent and independent autoreactive T-cell clones in primary biliary cirrhosis. Gastroenterology 125(5):1379–1387. doi:10.1016/S0016-5085(03)01359-310

    Article  PubMed  Google Scholar 

  12. Shimoda S, Miyakawa H, Nakamura M et al (2008) CD4 T-cell autoreactivity to the mitochondrial autoantigen PDC-E2 in AMA-negative primary biliary cirrhosis. J Autoimmun 31(2):110–115. doi:10.1016/j.jaut.2008.05.003

    Article  CAS  PubMed  Google Scholar 

  13. Masuda J, Omagari K, Ohba K et al (2003) Correlation between histopathological findings of the liver and IgA class antibodies to 2-oxo-acid dehydrogenase complex in primary biliary cirrhosis. Dig Dis Sci 48(5):932–938

    Article  CAS  PubMed  Google Scholar 

  14. Rigopoulou EI, Davies ET, Bogdanos DP et al (2007) Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary biliary cirrhosis. Liver Int 27(9):1226–1231. doi:10.1111/j.1478-3231.2007.01586.x

    Article  CAS  PubMed  Google Scholar 

  15. Bizzaro N, Covini G, Rosina F et al (2012) Overcoming a “probable” diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: study of 100 sera and review of the literature. Clin Rev Allergy Immunol 42(3):288–297. doi:10.1007/s12016-010-8234-y

    Article  CAS  PubMed  Google Scholar 

  16. Shimoda S, Nakamura M, Ishibashi H et al (2003) Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis. Gastroenterology 124(7):1915–1925. doi:10.1016/S0016-5085(03)00387-1

    Article  CAS  PubMed  Google Scholar 

  17. Fritzler MJ, Rattner JB, Luft LM et al (2011) Historical perspectives on the discovery and elucidation of autoantibodies to centromere proteins (CENP) and the emerging importance of antibodies to CENP-F. Autoimmun Rev 10(4):194–200. doi:10.1016/j.autrev.2010.09.025

    Article  CAS  PubMed  Google Scholar 

  18. Agmon-Levin N, Shapira Y, Selmi C et al (2010) A comprehensive evaluation of serum autoantibodies in primary biliary cirrhosis. J Autoimmun 34(1):55–58. doi:10.1016/j.jaut.2009.08.009

    Article  CAS  PubMed  Google Scholar 

  19. Muratori P, Granito A, Pappas G et al (2009) The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Am J Gastroenterol 104(6):1420–1425. doi:10.1038/ajg.2009.126

    Article  PubMed  Google Scholar 

  20. Hu C-J, Song G, Huang W et al (2012) Identification of new autoantigens for primary biliary cirrhosis using human proteome microarrays. Mol Cel Proteomics 11(9):669–680. doi:10.1074/mcp.M111.015529

    Article  CAS  Google Scholar 

  21. Stinton LM, Swain M, Myers RP et al (2011) Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis. Clin Exp Immunol 163(2):147–156. doi:10.1111/j.1365-2249.2010.04288.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Dellavance A, Cancado EL, Abrantes-Lemos CP et al (2013) Humoral autoimmune response heterogeneity in the spectrum of primary biliary cirrhosis. Hepatol Int 7(2):775–784. doi:10.1007/s12072-012-9413-0

    Article  PubMed Central  PubMed  Google Scholar 

  23. Mattalia A, Quaranta S, Leung P (1998) Characterization of antimitochondrial antibodies in healthy adults. Hepatology 27(3):656–661

    Article  CAS  PubMed  Google Scholar 

  24. Bellucci R, Oertelt S, Gallagher M et al (2007) Differential epitope mapping of antibodies to PDC-E2 in patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation and primary biliary cirrhosis. Blood 109(5):2001–2007. doi:10.1182/blood-2006-06-030304

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Leung PS, Rossaro L, Davis PA, Acute Liver Failure Study G et al (2007) Antimitochondrial antibodies in acute liver failure: implications for primary biliary cirrhosis. Hepatology 46(5):1436–1442. doi:10.1002/hep.21828

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Lazaridis KN, Juran BD, Boe GM et al (2007) Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis. Hepatology 46(3):785–792. doi:10.1002/hep.21749

    Article  PubMed  Google Scholar 

  27. Zografos TA, Gatselis N, Zachou K et al (2012) Primary biliary cirrhosis-specific autoantibodies in first degree relatives of Greek primary biliary cirrhosis patients. World J Gastroenterol 18(34):4721–4728. doi:10.3748/wjg.v18.i34.4721

    Article  PubMed Central  PubMed  Google Scholar 

  28. Lassoued K, Guilly M, Andre C (1988) Autoantibodies to 200kD polypeptide(s) of the nuclear envelope- a new serologic marker of primary biliary cirrhosis. Clin Exp Immunol 74:283–288

    CAS  PubMed Central  PubMed  Google Scholar 

  29. Lozano F, Pares A, Borche L et al (1988) Autoantibodies against nuclear envelope-associated proteins in primary biliary cirrhosis. Hepatology 8(4):930–938

    Article  CAS  PubMed  Google Scholar 

  30. Courvalin J-C, Lassoued K, Bartnik E et al (1990) The 210-kD nuclear envelope polypeptide recognized by human autoantibodies in primary biliary cirrhosis is the major glycoprotein of the nuclear pore. J Clin Invest 86(7):279–285

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Itoh S, Ichida T, Yoshida T et al (1998) Autoantibodies against 210 kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis. J Gastro Hepatol 13:257–265

    Article  CAS  Google Scholar 

  32. Miyachi K, Hankins RW, Matsushima H et al (2003) Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study. J Autoimmun 20(3):247–254. doi:10.1016/s0896-8411(03)00033-7

    Article  CAS  PubMed  Google Scholar 

  33. Invernizzi P, Podda M, Battezzati PM et al (2001) Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis. J Hepatol 34:366–372

    Article  CAS  PubMed  Google Scholar 

  34. Muratori P, Muratori L, Ferrari R et al (2003) Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Am J Gastroenterol 98(2):431–437. doi:10.1016/s0002-9270(02)05925-7

    Article  PubMed  Google Scholar 

  35. Nakamura M, Shimizu-Yoshida Y, Takii Y et al (2005) Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis. J Hepatol 42(3):386–392. doi:10.1016/j.jhep.2004.11.016

    Article  CAS  PubMed  Google Scholar 

  36. Wesierska-Gadek J, Penner E, Battezzati PM et al (2006) Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis. Hepatology 43(5):1135–1144. doi:10.1002/hep.21172

    Article  CAS  PubMed  Google Scholar 

  37. Gao L, Tian X, Liu B, Zhang F (2008) The value of antinuclear antibodies in primary biliary cirrhosis. Clin Exp Med 8(1):9–15. doi:10.1007/s10238-008-0150-6

    Article  CAS  PubMed  Google Scholar 

  38. Sfakianaki O, Koulentaki M, Tzardi M et al (2010) Peri-nuclear antibodies correlate with survival in Greek primary biliary cirrhosis patients. World J Gastroenterol 16:4938–4943

    Article  PubMed Central  PubMed  Google Scholar 

  39. Yang W-H, Yu J, Nakajima A et al (2004) Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure? Clin Gastro Hepatol 2(12):1116–1122

    Article  Google Scholar 

  40. Poupon R (2010) Primary biliary cirrhosis—a 2010 update. J Hepatol 52:745–758

    Article  PubMed  Google Scholar 

  41. Rigamonti C, Shand LM, Feudjo M et al (2006) Clinical features and prognosis of primary biliary cirrhosis associated with systemic sclerosis. Gut 55(3):388–394. doi:10.1136/gut.2005.075002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Shi TY, Zhang LN, Chen H et al (2013) Risk factors for hepatic decompensation in patients with primary biliary cirrhosis. World J Gastroenterol 19(7):1111–1118. doi:10.3748/wjg.v19.i7.1111

    Article  PubMed Central  PubMed  Google Scholar 

  43. Mytilinaiou MG, Meyer W, Scheper T et al (2012) Diagnostic and clinical utility of antibodies against the nuclear body promyelocytic leukaemia and Sp100 antigens in patients with primary biliary cirrhosis. Clin Chim Acta 413(15–16):1211–1216. doi:10.1016/j.cca.2012.03.020

    Article  CAS  PubMed  Google Scholar 

  44. Nakamura M, Ito M, Yamamoto K et al (2011) Positive anti-GP210 antibodies is a risk factor for poor biochemical response to ursodeoxycholic acid treatment in Japanese patients with primary biliary cirrhosis. J Hepatol 54(Suppl 1):S514–S515

    Article  Google Scholar 

  45. Nakamura M, Yasunami M, Kondo H, PBC Study Group in NHOSLJ* et al (2010) Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): the HLA-DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC. Hepatol Res 40(5):494–504. doi:10.1111/j.1872-034X.2010.00631.x

    Article  PubMed  Google Scholar 

  46. Umemura T, Joshita S, Ichijo T, Shinshu PBC Study Group et al (2012) Human leukocyte antigen class II molecules confer both susceptibility and progression in Japanese patients with primary biliary cirrhosis. Hepatology 55(2):506–511. doi:10.1002/hep.24705

    Article  CAS  PubMed  Google Scholar 

  47. Zhao DT, Liao HY, Zhang X et al (2014) Human leucocyte antigen alleles and haplotypes and their associations with antinuclear antibodies features in Chinese patients with primary biliary cirrhosis. Liver Int 34(2):220–226. doi:10.1111/liv.12236

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Clinical Research Center, National Hospital Organization Nagasaki Medical Center, Kubara 2-1001-1, Omura City, Nagasaki, 856-8562, Japan

    Atsumasa Komori

  2. Department of Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Kubara 2-1001-1, Omura City, Nagasaki, 856-8562, Japan

    Atsumasa Komori

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  1. Atsumasa Komori
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Correspondence to Atsumasa Komori .

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  1. Dept of Gastroenterology & Rheumatology, Fukushima Medical University of Medicine, Fukushima, Japan

    Hiromasa Ohira

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Komori, A. (2014). Autoantibodies in Primary Biliary Cirrhosis. In: Ohira, H. (eds) Autoimmune Liver Diseases. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54789-1_17

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  • DOI: https://doi.org/10.1007/978-4-431-54789-1_17

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