Journal Home > Volume 1 , Issue 2

Autoantibody (AAb) detection has become one of the standards of diagnosis for autoimmune liver disease (AILD), and some AAbs have become specific biomarkers of AILD. In addition, AAbs can be detected in patients with non‐AILDs, such as viral hepatitis and alcoholic liver disease. However, the distribution characteristics and pathogenic mechanisms of AAbs in patients with non‐AILD are unclear. This article summarizes the characteristics of AAbs in several common clinical chronic liver diseases (CLDs) and discusses the value of AAb analysis in CLD.


menu
Abstract
Full text
Outline
About this article

Application of autoantibody detection in chronic liver disease

Show Author's information Jinyu Han1Jin Chen2Yajie Wang1,2( )
Peking University Ditan Teaching Hospital, Beijing, China
Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing, China

Abstract

Autoantibody (AAb) detection has become one of the standards of diagnosis for autoimmune liver disease (AILD), and some AAbs have become specific biomarkers of AILD. In addition, AAbs can be detected in patients with non‐AILDs, such as viral hepatitis and alcoholic liver disease. However, the distribution characteristics and pathogenic mechanisms of AAbs in patients with non‐AILD are unclear. This article summarizes the characteristics of AAbs in several common clinical chronic liver diseases (CLDs) and discusses the value of AAb analysis in CLD.

Keywords: hepatitis B virus, alcoholic liver disease, autoantibody, autoimmune liver disease

References(45)

[1]

Xiao ZX, Miller JS, Zheng SG. An updated advance of autoantibodies in autoimmune disease. Autoimmun Rev. 2021;20(2):102743. https://doi.org/10.1016/j.autrev.2020.102743

[2]

Engel B, Taubert R, Jaeckel E, Manns MP. The future of autoimmune liver diseases – understanding pathogenesis and improving morbidity and mortality. Liver Int. 2020;40(Suppl 1):149–53. https://doi.org/10.1111/liv.14378

[3]

Komori A. Recent updates on the management of autoimmune hepatitis. Clin Mol Hepatol. 2021;27(1):58–69. https://doi.org/10.3350/cmh.2020.0189

[4]

Terziroli Beretta‐Piccoli B, Mieli‐Vergani G, Vergani D. Autoimmmune hepatitis. Cell Mol Immunol. 2022;19(2):158–76. https://doi.org/10.1038/s41423-021-00768-8

[5]

Ahmad A, Heijke R, Eriksson P, Wirestam L, Kechagias S, Dahle C, et al. Autoantibodies associated with primary biliary cholangitis are common among patients with systemic lupus erythematosus even in the absence of elevated liver enzymes. Clin Exp Immunol. 2021;203(1):22–31. https://doi.org/10.1111/cei.13512

[6]

Sebode M, Weiler‐Normann C, Liwinski T, Schramm C. Autoantibodies in autoimmune liver disease— clinical and diagnostic relevance. Front Immunol. 2018;9:609. https://doi.org/10.3389/fimmu.2018.00609

[7]

Irure‐Ventura J, López‐Hoyos M. The past, present, and future in antinuclear antibodies (ANA). Diagnostics. 2022;12(3):647. https://doi.org/10.3390/diagnostics12030647

[8]

Nakamura RM, Tan EM. Recent progress in the study of autoantibodies to nuclear antigens. Hum Pathol. 1978;9(1):85–91. https://doi.org/10.1016/S0046-8177(78)80010-0

[9]

Nakamura RM, Tan EM. Recent advances in laboratory tests and the significance of autoantibodies to nuclear antigens in systemic rheumatic diseases. Clin Lab Med. 1986;6(1):41–53. https://doi.org/10.1016/S0272-2712(18)30825-4

[10]

Cowling DC, Mackay IR, Taft LI. Lupoid hepatitis. Lancet. 1956;271(6957):1323–6. https://doi.org/10.1016/S0140-6736(56)91483-0

[11]

Liberal R, Mieli‐Vergani G, Vergani D. Clinical significance of autoantibodies in autoimmune hepatitis. J Autoimmun. 2013;46:17–24. https://doi.org/10.1016/j.jaut.2013.08.001

[12]

Whittingham S, Irwin J, Mackay IR, Smalley M. Smooth muscle autoantibody in “autoimmune” hepatitis. Gastroenterology. 1966;51(4):499–505. https://doi.org/10.1016/S0016-5085(19)34365-3

[13]

Cotler SJ, Kanji K, Keshavarzian A, Jensen DM, Jakate S. Prevalence and significance of autoantibodies in patients with non‐alcoholic steatohepatitis. J Clin Gastroenterol. 2004;38(9):801–4. https://doi.org/10.1097/01.mcg.0000139072.38580.a0

[14]

Vergani D, Alvarez F, Bianchi FB, Cancado EL, Mackay IR, Manns MP, et al. Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the international autoimmune hepatitis group. J Hepatol. 2004;41(4):677–83. https://doi.org/10.1016/j.jhep.2004.08.002

[15]

Gueguen M, Meunier‐Rotival M, Bernard O, Alvarez F. Anti‐liver kidney microsome antibody recognizes a cytochrome P450 from the IID subfamily. J Exp Med. 1988;168(2):801–6. https://doi.org/10.1084/jem.168.2.801

[16]

Manns MP, Griffin KJ, Sullivan KF, Johnson EF. LKM‐1 autoantibodies recognize a short linear sequence in P450IID6, a cytochrome P‐450 monooxygenase. J Clin Invest. 1991;88(4):1370–8. https://doi.org/10.1172/JCI115443

[17]

Manns MP, Johnson EF, Griffin KJ, Tan EM, Sullivan KF. Major antigen of liver kidney microsomal autoantibodies in idiopathic autoimmune hepatitis is cytochrome P450db1. J Clin Invest. 1989;83(3):1066–72. https://doi.org/10.1172/JCI113949

[18]

Lenzi M, Manotti P, Muratori L, Cataleta M, Ballardini G, Gassani F, et al. Liver cytosolic 1 antigen‐antibody system in type 2 autoimmune hepatitis and hepatitis C virus infection. Gut. 1995;36(5):749–54. https://doi.org/10.1136/gut.36.5.749

[19]

Lu M, Zhou Y, Haller IV, Romanelli RJ, VanWormer JJ, Rodriguez CV, et al. Increasing prevalence of primary biliary cholangitis and reduced mortality with treatment. Clin Gastroenterol Hepatol. 2018;16(8):1342–50. https://doi.org/10.1016/j.cgh.2017.12.033

[20]

Beuers U, Gershwin ME, Gish RG, Invernizzi P, Jones DE, Lindor K, et al. Changing nomenclature for PBC: From ‘cirrhosis’ to ‘cholangitis’. Clin Res Hepatol Gastroenterol. 2015;39(5):e57–e5959. https://doi.org/10.1136/gutjnl-2015-310593

[21]

Selmi C, Balkwill DL, Invernizzi P, Ansari AA, Coppel RL, Podda M, et al. Patients with primary biliary cirrhosis react against a ubiquitous xenobiotic‐metabolizing bacterium. Hepatology. 2003;38(5):1250–7. https://doi.org/10.1053/jhep.2003.50446

[22]

Walker JG, Doniach D, Roitt IM, Sherlock S. Serological tests in diagnosis of primary biliary cirrhosis. Lancet. 1965;1(7390):827–31. https://doi.org/10.1016/S0140-6736(65)91372-3

[23]

Berg PA, Klein R. Antimitochondrial antibodies in primary biliary cirrhosis and other disorders: definition and clinical relevance. Dig Dis. 1992;10(2):85–101. https://doi.org/10.1159/000171347

[24]

Muratori L, Granito A, Muratori P, Pappas G, Bianchi FB. Antimitochondrial Antibodies and other antibodies in primary biliary cirrhosis: diagnostic and prognostic value. Clin Liver Dis. 2008;12(2):261–76. https://doi.org/10.1016/j.cld.2008.02.009

[25]

Poyatos E, Morandeira F, Climent J, Mas V, Castellote J, Bas J. Detection of anti‐mitochondrial 2‐oxoacid dehydrogenase complex subunit’s antibodies for the diagnosis of primary biliary cholangitis. Clinical Immunol. 2021:108749. https://doi.org/10.1016/j.clim.2021.108749

[26]

Tana MM, Shums Z, Milo J, Norman GL, Leung PS, Gershwin ME, et al. The significance of autoantibody changes over time in primary biliary cirrhosis. Am J Clin Pathol. 2015;144(4):601–6. https://doi.org/10.1309/AJCPQV4A7QAEEFEV

[27]

Ruffatti A, Arslan P, Floreani A, De Silvestro G, Calligaro A, Naccarato R, et al. Nuclear membrane‐staining antinuclear antibody in patients with primary biliary cirrhosis. J Clin Immunol. 1985;5(5):357–61. https://doi.org/10.1007/BF00918255

[28]

Bandin O, Courvalin JC, Poupon R, Dubel L, Homberg JC, Johanet C. Specificity and sensitivity of gp210 autoantibodies detected using an enzyme‐linked immunosorbent assay and a synthetic polypeptide in the diagnosis of primary biliary cirrhosis. Hepatology. 1996;23(5):1020–4. https://doi.org/10.1002/hep.510230512

[29]

Rigamonti C, Shand LM, Feudjo M, Bunn CC, Black CM, Denton CP, et al. Clinical features and prognosis of primary biliary cirrhosis associated with systemic sclerosis. Gut. 2006;55(3):388–94. https://doi.org/10.1136/gut.2005.075002

[30]

Nakamura M, Kondo H, Mori T, Komori A, Matsuyama M, Ito M, et al. Anti‐gp210 and anti‐centromere antibodies are different risk factors for the progression of primary biliary cirrhosis. Hepatology. 2007;45(1):118–27. https://doi.org/10.1002/hep.21472

[31]

Liberal R, Grant CR, Sakkas L, Bizzaro N, Bogdanos DP. Diagnostic and clinical significance of anti‐centromere antibodies in primary biliary cirrhosis. Clin Res Hepatol Gastroenterol. 2013;37(6):572–85. https://doi.org/10.1016/j.clinre.2013.04.005

[32]

Honda A, Ikegami T, Matsuzaki Y. Anti‐gp210 and anti‐centromere antibodies for the prediction of PBC patients with an incomplete biochemical response to UDCA and bezafibrate. Hepatol Res. 2015;45(8):827–8. https://doi.org/10.1111/hepr.12461

[33]

Mandai S, Kanda E, Arai Y, Hirasawa S, Hirai T, Aki S, et al. Anti‐centromere antibody is an independent risk factor for chronic kidney disease in patients with primary biliary cirrhosis. Clin Exp Nephrol. 2013;17(3):405–10. https://doi.org/10.1007/s10157-012-0724-1

[34]

Lee YM, Kaplan MM. Primary sclerosing cholangitis. N Engl J Med. 1995;332(14):924–33. https://doi.org/10.1056/NEJM199504063321406

[35]

Kaplan GG, Laupland KB, Butzner D, Urbanski SJ, Lee SS. The burden of large and small duct primary sclerosing cholangitis in adults and children: a population‐based analysis. Am J Gastroenterol. 2007;102(5):1042–9. https://doi.org/10.1111/j.1572-0241.2007.01103.x

[36]

Dave M, Elmunzer BJ, Dwamena BA, Higgins PD. Primary sclerosing cholangitis: meta‐analysis of diagnostic performance of MR cholangiopancreatography. Radiology. 2010;256(2):387–96. https://doi.org/10.1148/radiol.10091953

[37]

Lindor KD, Kowdley KV, Harrison ME, American College of Gastroenterology. ACG clinical guideline: primary sclerosing cholangitis. Am J Gastroenterol. 2015;110(5):646–59. https://doi.org/10.1038/ajg.2015.112

[38]

European Association for the Study of the Liver. EASL clinical practice guidelines: management of cholestatic liver diseases. J Hepatol. 2009;51(2):237–67. https://doi.org/10.1016/j.jhep.2009.04.009

[39]

Pokorny CS, Norton ID, McCaughan GW, Selby WS. Anti‐neutrophil cytoplasmic antibody: a prognostic indicator in primary sclerosing cholangitis. J Gastroenterol Hepatol. 1994;9(1):40–4. https://doi.org/10.1111/j.1440-1746.1994.tb01214

[40]

Liang TJ. Hepatitis B: the virus and disease. Hepatology. 2009;49(5 Suppl):S13–S21. https://doi.org/10.1002/hep.22881

[41]

Bogdanos DP, Mieli‐Vergani G, Vergani D. Virus, liver and autoimmunity. Dig Liver Dis. 2000;32(5):440–6. https://doi.org/10.1016/S1590-8658(00)80266-2

[42]

Maya R, Gershwin ME, Shoenfeld Y. Hepatitis B virus (HBV) and autoimmune disease. Clin Rev Allergy Immunol. 2008;34(1):85–102. https://doi.org/10.1007/s12016-007-8013-6

[43]

Hsu TC, Tsay GJ, Chen TY, Liu YC, Tzang BS. Anti‐PCNA autoantibodies preferentially recognize C‐terminal of PCNA in patients with chronic hepatitis B virus infection. Clin Exp Immunol. 2006;144(1):110–6. https://doi.org/10.1111/j.1365-2249.2006.03046.x

[44]

Min L, Jing H, Li S, De Kai Q. Prevalence and significance of autoantibodies in patients with alcoholic liver disease. J Dig Dis. 2013;14(7):396–401. https://doi.org/10.1111/1751-2980.12057

[45]

Marcellin P, Kutala B. Liver diseases: a major, neglected global public health problem requiring urgent actions and large scale screening. Liver Int. 2018;38(Suppl 1):2–6. https://doi.org/10.1111/liv.13682

Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 03 April 2023
Accepted: 25 April 2023
Published: 14 June 2023
Issue date: September 2023

Copyright

© 2023 The Authors. Tsinghua University Press.

Acknowledgements

ACKNOWLEDGMENTS

We thank all the colleagues in our laboratory for insightful suggestions and discussion on the manuscript.

Rights and permissions

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Return