Anti-mitochondrial M2 antibody-positive autoimmune hepatitis

Tomizawa,Minoru; Shinozaki,Fuminobu; Fugo,Kazunori; Motoyoshi,Yasufumi; Sugiyama,Takao; Yamamoto,Shigenori; Kishimoto,Takashi; Ishige,Naoki

doi:10.3892/etm.2015.2694

Anti-mitochondrial M2 antibody-positive autoimmune hepatitis

Authors:
- Minoru Tomizawa
- Fuminobu Shinozaki
- Kazunori Fugo
- Yasufumi Motoyoshi
- Takao Sugiyama
- Shigenori Yamamoto
- Takashi Kishimoto
- Naoki Ishige
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Affiliations: Department of Gastroenterology, National Hospital Organization Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Radiology, National Hospital Organization Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Molecular Pathology, Chiba University Graduate School of Medicine, Chiba, Chiba 260‑8670, Japan, Department of Neurology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Rheumatology, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Pediatrics, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan, Department of Neurosurgery, National Hospital Organization, Shimoshizu Hospital, Yotsukaido, Chiba 284‑0003, Japan
Published online on: August 20, 2015 https://doi.org/10.3892/etm.2015.2694
Pages: 1419-1422

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Abstract

Anti-mitochondrial M2 antibody (AMA-M2) is specific to primary biliary cirrhosis (PBC), but can also be found in certain patients with autoimmune hepatitis (AIH). Effective methods of differentiating between PBC and AIH are required, as their clinical course and management are different. Titers of AMA‑M2 were analyzed before and after follow‑up in patients with PBC or AIH. Patients who underwent liver biopsy and were diagnosed with either AIH (10 patients) or PBC (3 patients) were enrolled in the study. The AMA‑M2 antibody titers of these patients were analyzed upon hospital admission. AMA‑M2 reacted with the pyruvate dehydrogenase complex‑E2, branched‑chain 2‑oxo acid dehydrogenase complex and 2‑oxoglutaric acid dehydrogenase complex in the assay utilized for this study. The cut‑off value for AMA‑M2 was 5. Six AIH patients were AMA‑M2(‑) and 4 were AMA‑M2(+). The titer for the AIH patients who were AMA‑M2(+) was 24.8±14.8, compared with 324±174 in the patients with PBC (P=0.0138). Three AMA‑M2(+) AIH patients were followed‑up after liver biopsy. The AMA‑M2 levels had decreased in all 3 patients, becoming undetectable in 2 of them. In conclusion, certain patients with AIH in this study were found to be AMA‑M2(+), but the titers were significantly lower than those in the patients with PBC. At follow-up, the AIH patients exhibited decreased AMA-M2 titers.

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1	Liberal R, Grant CR, Mieli-Vergani G and Vergani D: Autoimmune hepatitis: A comprehensive review. J Autoimmun. 41:126–139. 2013. View Article : Google Scholar : PubMed/NCBI
2	Liberal R, Mieli-Vergani G and Vergani D: Clinical significance of autoantibodies in autoimmune hepatitis. J Autoimmun. 46:17–24. 2013. View Article : Google Scholar : PubMed/NCBI
3	Krawitt EL: Autoimmune hepatitis. N Engl J Med. 354:54–66. 2006. View Article : Google Scholar : PubMed/NCBI
4	Oketani M, Ido A, Nakayama N, Takikawa Y, Naiki T, Yamagishi Y, Ichida T, Mochida S, Onishi S and Tsubouchi H: Intractable Hepato-Biliary Diseases Study Group Of Japan: Etiology and prognosis of fulminant hepatitis and late-onset hepatic failure in Japan: Summary of the annual nationwide survey between 2004 and 2009. Hepatol Res. 43:97–105. 2013. View Article : Google Scholar : PubMed/NCBI
5	Czaja AJ: Acute and acute severe (fulminant) autoimmune hepatitis. Dig Dis Sci. 58:897–914. 2013. View Article : Google Scholar : PubMed/NCBI
6	Montano Loza, Carpenter HA and Czaja AJ: Predictive factors for hepatocellular carcinoma in type 1 autoimmune hepatitis. Am J Gastroenterol. 103:1944–1951. 2008. View Article : Google Scholar : PubMed/NCBI
7	Yoshizawa K, Matsumoto A, Ichijo T, Umemura T, Joshita S, Komatsu M, Tanaka N, Tanaka E, Ota M, Katsuyama Y, et al: Long-term outcome of Japanese patients with type 1 autoimmune hepatitis. Hepatology. 56:668–676. 2012. View Article : Google Scholar : PubMed/NCBI
8	Bowlus CL and Gershwin ME: The diagnosis of primary biliary cirrhosis. Autoimmun Rev. 13:441–444. 2014. View Article : Google Scholar : PubMed/NCBI
9	Kakuda Y, Harada K, Sawada-Kitamura S, Ikeda H, Sato Y, Sasaki M, Okafuji H, Mizukoshi E, Terasaki S, Ohta H, et al: Evaluation of a new histologic staging and grading system for primary biliary cirrhosis in comparison with classical systems. Hum Pathol. 44:1107–1117. 2013. View Article : Google Scholar : PubMed/NCBI
10	Manns MP, Czaja AJ, Gorham JD, Krawitt EL, Mieli-Vergani G, Vergani D and Vierling JM: American Association For The Study Of Liver Diseases: Diagnosis and management of autoimmune hepatitis. Hepatology. 51:2193–2213. 2010. View Article : Google Scholar : PubMed/NCBI
11	Verslype C, George C, Buchel E, Nevens F, van Steenbergen W and Fevery J: Diagnosis and treatment of autoimmune hepatitis at age 65 and older. Aliment Pharmacol Ther. 21:695–699. 2005. View Article : Google Scholar : PubMed/NCBI
12	Chantran Y, Ballot É and Johanet C: Autoantibodies in primary biliary cirrhosis: Antimitochondrial autoantibodies. Clin Res Hepatol Gastroenterol. 37:431–433. 2013. View Article : Google Scholar : PubMed/NCBI
13	Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV and Heathcote EJ: American Association For Study Of Liver Diseases: Primary biliary cirrhosis. Hepatology. 50:291–308. 2009. View Article : Google Scholar : PubMed/NCBI
14	Gershwin ME, Mackay IR, Sturgess A and Coppel RL: Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis. J Immunol. 138:3525–3531. 1987.PubMed/NCBI
15	Czaja AJ, Carpenter HA, Santrach PJ, Moore SB and Homburger HA: The nature and prognosis of severe cryptogenic chronic active hepatitis. Gastroenterology. 104:1755–1761. 1993.PubMed/NCBI
16	Moteki S, Leung PS, Dickson ER, Van Thiel DH, Galperin C, Buch T, Alarcon-Segovia D, Kershenobich D, Kawano K, Coppel RL, et al: Epitope mapping and reactivity of autoantibodies to the E2 component of 2-oxoglutarate dehydrogenase complex in primary biliary cirrhosis using recombinant 2-oxoglutarate dehydrogenase complex. Hepatology. 23:436–444. 1996. View Article : Google Scholar : PubMed/NCBI
17	Gershwin ME, Rowley M, Davis PA, Leung P, Coppel R and Mackay IR: Molecular biology of the 2-oxo-acid dehydrogenase complexes and anti-mitochondrial antibodies. Prog Liver Dis. 10:47–61. 1992.PubMed/NCBI
18	Leung PS, Chuang DT, Wynn RM, Cha S, Danner DJ, Ansari A, Coppel RL and Gershwin ME: Autoantibodies to BCOADC-E2 in patients with primary biliary cirrhosis recognize a conformational epitope. Hepatology. 22:505–513. 1995. View Article : Google Scholar : PubMed/NCBI
19	Yamagiwa S, Kamimura H, Takamura M and Aoyagi Y: Autoantibodies in primary biliary cirrhosis: Recent progress in research on the pathogenetic and clinical significance. World J Gastroenterol. 20:2606–2612. 2014. View Article : Google Scholar : PubMed/NCBI
20	Yamamoto K, Terada R, Okamoto R, Hiasa Y, Abe M, Onji M and Tsuji T: A scoring system for primary biliary cirrhosis and its application for variant forms of autoimmune liver disease. J Gastroenterol. 38:52–59. 2003. View Article : Google Scholar : PubMed/NCBI
21	Farias AQ, Gonçalves LL, Bittencourt PL, De Melo ES, Abrantes-Lemos CP, Porta G, Nakhle MC, Carrilho FJ and Cancado EL: Applicability of the IAIHG scoring system to the diagnosis of antimitochondrial/anti-M2 seropositive variant form of autoimmune hepatitis. J Gastroenterol Hepatol. 21:887–893. 2006. View Article : Google Scholar : PubMed/NCBI
22	Suzuki A, Brunt EM, Kleiner DE, Miquel R, Smyrk TC, Andrade RJ, Lucena MI, Castiella A, Lindor K and Björnsson E: The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury. Hepatology. 54:931–939. 2011. View Article : Google Scholar : PubMed/NCBI
23	Alvarez F, Berg PA, Bianchi FB, Bianchi L, Burroughs AK, Cancado EL, Chapman RW, Cooksley WG, Czaja AJ, Desmet VJ, et al: International autoimmune hepatitis group report: Review of criteria for diagnosis of autoimmune hepatitis. J Hepatol. 31:929–938. 1999. View Article : Google Scholar : PubMed/NCBI
24	Chazouilleres O, Wendum D, Serfaty L, Montembault S, Rosmorduc O and Poupon R: Primary biliary cirrhosis-autoimmune hepatitis overlap syndrome: Clinical features and response to therapy. Hepatology. 28:296–301. 1998. View Article : Google Scholar : PubMed/NCBI
25	Dellavance A, Cancado EL, Abrantes-Lemos CP, Harriz M, Marvulle V and Andrade LE: Humoral autoimmune response heterogeneity in the spectrum of primary biliary cirrhosis. Hepatol Int. 7:775–784. 2012. View Article : Google Scholar : PubMed/NCBI
26	Miyakawa H, Kitazawa E, Fujikawa H, Kikuchi K, Abe K, Kawaguchi N and Kako M: Analysis of two major anti-M2 antibodies (anti-PDC-E2/anti-BCOADC-E2) in primary biliary cirrhosis: Relationship to titers of immunofluorescent anti-mitochondrial antibody. Hepatol Res. 18:1–9. 2000. View Article : Google Scholar : PubMed/NCBI
27	Yanagawa T, Miyakawa H, Shibata M, Kawaguchi N, Ishibashi M, Goto N and Mitamura K: Immunoreactivity to pyruvate dehydrogenase complex-E2 in well-defined patients with autoimmune hepatitis: Western blot analysis. Hepatol Res. 26:81–86. 2003. View Article : Google Scholar : PubMed/NCBI
28	Roda A, Pasini P, Guardigli M, Baraldini M, Musiani M and Mirasoli M: Bio- and chemiluminescence in bioanalysis. Fresenius J Anal Chem. 366:752–759. 2000. View Article : Google Scholar : PubMed/NCBI
29	O'Brien C, Joshi S, Feld JJ, Guindi M, Dienes HP and Heathcote EJ: Long-term follow-up of antimitochondrial antibody-positive autoimmune hepatitis. Hepatology. 48:550–556. 2008. View Article : Google Scholar : PubMed/NCBI