Lab Med Online.  2014 Apr;4(2):91-97.

A Comparative Evaluation of the Performances of Anti-MIT3, Anti-gp210, and Anti-sp100 Antibodies for the Diagnosis of Primary Biliary Cirrhosis

Affiliations
  • 1Department of Laboratory Medicine, Hallym University College of Medicine, Anyang, Korea. kangheejung@hallym.or.kr
  • 2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hallym University College of Medicine, Anyang, Korea.

Abstract

BACKGROUND
Anti-mitochondrial antibody (AMA) is a serological hallmark of primary biliary cirrhosis (PBC). AMAs are detected by an immunofluorescence assay (IF), which is subject to errors. We evaluated the diagnostic performances of the AMA ELISA test (the anti-MIT3 antibody) and PBC-associated antinuclear antibody (ANA) tests (the anti-gp210 and anti-sp100 antibodies).
METHODS
AMA, anti-gp210, and anti-sp100 were measured in the sera of 130 subjects including patients for whom the AMA test was requested with the clinical suspicion of PBC, patients with other autoimmune diseases, and those undergoing health check-ups. AMA was detected by both IF and ELISA (anti-MIT3 antibodies), and anti-gp210 and anti-sp100 were detected by ELISA. The diagnostic performances of the anti-MIT3, anti-gp210, and anti-sp100 were compared with that of the AMA IF test. Associations between the presence of anti-sp100 or anti-gp210 and the diagnosis and biochemical abnormalities of PBC were investigated.
RESULTS
The area under the curve of anti-MIT3 for the diagnosis of PBC was 0.934 (95% confidence interval, 0.877-0.970), and the agreement between anti-MIT3 and AMA IF was 93.8% (kappa, 0.82). The sensitivities of anti-MIT3 and AMA IF were both 100%, and the specificities were 83.1% and 81.4%, respectively, whereas the sensitivities of anti-gp210 and anti-sp100 were 41.7% and 16.7%, and their specificities were 94.9% and 97.5%, respectively. The presence of anti-gp210 was associated with the diagnosis of PBC (P=0.0001), but that of anti-sp100 was not.
CONCLUSIONS
The diagnostic performance of anti-MIT3 is comparable to that of AMA IF. Anti-gp210 seems to be complementary to AMA for the diagnosis of PBC.

Keyword

anti-MIT3; AMA; PBC; anti-gp210; anti-sp100

MeSH Terms

Antibodies*
Antibodies, Antinuclear
Autoimmune Diseases
Diagnosis*
Enzyme-Linked Immunosorbent Assay
Fluorescent Antibody Technique
Humans
Liver Cirrhosis, Biliary*
Antibodies
Antibodies, Antinuclear

Figure

  • Fig. 1 Receiver operating characteristics curve for anti-MIT3 in the patients with PBC. The area under the curve of the anti-MIT3 is 0.934. The arrow indicates optimum cut-off value.


Reference

1. Talwalkar JA, Lindor KD. Primary biliary cirrhosis. Lancet. 2003; 362:53–61.
Article
2. Kaplan MM, Gershwin ME. Primary biliary cirrhosis. N Engl J Med. 2005; 353:1261–1273.
Article
3. Chon CY, Park JY. Primary biliary cirrhosis. Korean J Hepatol. 2006; 12:364–372.
4. Nishio A, Keeffe EB, Ishibashi H, Gershwin EM. Diagnosis and treatment of primary biliary cirrhosis. Med Sci Monit. 2000; 6:181–193.
5. Leuschner U. Primary biliary cirrhosis-presentation and diagnosis. Clin Liver Dis. 2003; 7:741–758.
Article
6. Kim KH, Han JY, Kim JM, Jang JS, Lee SW, Lee JH, et al. Determination of anti-mitochondrial antibody with M2 antigens. Korean J Lab Med. 2005; 25:104–110.
7. Berg PA, Klein R, Lindenborn-Fotinos J. Antimitochondrial antibodies in primary biliary cirrhosis. J Hepatol. 1986; 2:123–131.
Article
8. Hohenester S, Oude-Elferink RP, Beuers U. Primary biliarcirrhosis. Semin Immunopathol. 2009; 31:283–307.
9. Muratori P, Muratori L, Gershwin ME, Czaja AJ, Pappas G, MacCariello S, et al. 'True' antimitochondrial antibody-negative primary biliary cirrhosis, low sensitivity of the routine assays, or both? Clin Exp Immunol. 2004; 135:154–158.
Article
10. Miyakawa H, Tanaka A, Kikuchi E, Matusushita M, Kitazawa E, Kawaguchi N, et al. Detection of antimitochondrial autoantibodies in immunofluorescent AMA-negative patients with primary biliary cirrhosis using recombinant autoantigens. Hepatology. 2001; 34:243–248.
Article
11. Muratori P, Muratori L, Cassani F, Terlizzi P, Lenzi M, Rodrigo L, et al. Anti-multiple nuclear dots (anti-MND) and anti-SP100 antibodies in hepatic and rheumatological disorders. Clin Exp Immunol. 2002; 127:172–175.
Article
12. Invernizzi P, Podda M, Battezzati PM, Crosignani A, Zuin M, Hitchman E, et al. Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis. J Hepatol. 2001; 34:366–372.
Article
13. Muratori P, Muratori L, Ferrari R, Cassani F, Bianchi G, Lenzi M, et al. Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Am J Gastroenterol. 2003; 98:431–437.
Article
14. Nakamura M, Kondo H, Mori T, Komori A, Matsuyama M, Ito M, et al. Anti-gp210 and anticentromere antibodies are different risk factors for the progression of primary biliary cirrhosis. Hepatology. 2007; 45:118–127.
Article
15. Walker JG, Doniach D, Roitt IM, Sherlock S. Serological test in diagnosis of primary biliary cirrhosis. Lancet. 1965; 1:827–831.
16. Ishibashi H, Shimoda S, Gershwin ME. The immune response to mitochondrial autoantigens. Semin Liver Dis. 2005; 25:337–346.
Article
17. Bruggraber SF, Leung PS, Amano K, Quan C, Kurth MJ, Nantz MH, et al. Autoreactivity to lipoate and conjugated form of lipoate in primary biliary cirrhosis. Gastroenterology. 2003; 125:1705–1713.
Article
18. Zein CO, Angulo P, Lindor KD. When is liver biopsy needed in the diagnosis of primary biliary cirrhosis? Clin Gastroenterol Hepatol. 2003; 1:89–95.
Article
19. 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; 12:261–276.
Article
20. Bogdanos DP, Baum H, Vergani D. Antimitochondrial and other autoantibodies. Clin Liver Dis. 2003; 7:759–777.
Article
21. Nickowitz RE, Wozniak RW, Schaffner F, Worman HJ. Autoantibodies against integral membrane proteins of the nuclear envelope in patients with primary biliary cirrhosis. Gastroenterology. 1994; 106:193–199.
Article
22. Milkiewicz P, Buwaneswaran H, Coltescu C, Shums Z, Norman GL, Heathcote EJ. Value of autoantibody analysis in the differential diagnosis of chronic cholestatic liver disease. Clin Gastroenterol Hepatol. 2009; 7:1355–1360.
Article
23. Invernizzi P, Selmi C, Ranftler C, Podda M, Wesierska-Gadek J. Antinuclear antibodies in primary biliary cirrhosis. Semin Liver Dis. 2005; 25:298–310.
Article
25. Nakamura M, Shimizu-Yoshida Y, Takii Y, Komori A, Yokoyama T, Ueki T, et al. Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis. J Hepatol. 2005; 42:386–392.
Article
26. Worman HJ. Nuclear envelope protein autoantigens in primary biliary cirrhosis. Hepatol Res. 2007; 37:S3. S406–S411.
Article
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