Immunologic Research

, Volume 65, Issue 1, pp 299–306 | Cite as

Diagnostic accuracy of two tests for determination of anti-m2 in the diagnosis of primary biliary cirrhosis: Is it possible to predict the course of the disease?

  • Antonio Maria Alfano
  • Alessandra Romito
  • Cristiana Marchese
  • Marco Battistini
  • Giliola Crotti
  • Arturo Ferrini
  • Cristina Mancinetti
  • Tilde Manetta
  • Giulio Mengozzi
  • Paola Merlach
  • Marco Migliardi
  • Maria Teresa Tambuzzo
Mechanism in Autoimmunity

Abstract

To evaluate the analytical agreement between results obtained from the indirect immunofluorescence methods and from the multiplexed line-blot assay and EliA-M2, to analyze the diagnostic accuracy in a cohort of primary biliary cirrhosis (PBC) patients and in control patients of two different types of tests for anti-M2 and assess whether, with the advent of a quantitative test, the possibility exists to correlate disease activity with the value of AMA. Serum analysis of 67 patients with fluorescence patterns detected on Hep-2 cells suggestive of PBC-related antibodies and three groups of patients (15 PBC, 16 PBC suspect and 48 disease controls) was carried out. All samples were tested by both a qualitative test multiplexed line-blot Autoimmune Liver Disease Profile Euroline and by a quantitative test EliA-M2 IgG. In order to evaluate a possible correlation between the quantitative M2 and disease activity, we divided patients mixed in a further three groups based on the value EliA-M2. For each of these groups were calculated the average values of the main indices of cholestasis. A perfect agreement was shown between the EliA-M2 and the multiplexed line-blot method for AMA detection. All sera of patients with PBC were positive with both tests, with a 100 % sensitivity. Forty-seven of the 48 sera of the control group were negative for both tests with a 100 % next specificity, and only 70 % for the AMA-IIF. We had also observed in the other three groups of patients that the average of the values of γ–glutamyl transpeptidase and alkaline phosphatase increases with the increase of the value EliA-M2. The difference between the mean values of the most significant parameter which the alkaline phosphatase of the three groups is significant, with a statistically significant difference between the first and the third group (p value 0.023). Both the qualitative method Profile Euroline and the quantitative EliA-M2 have a high diagnostic accuracy for PBC, with a specificity higher than the immunofluorescence method. These preliminary data might suggest the possibility of using the dosage EliA-M2 not only in the diagnosis phase but also in the monitoring of disease activity.

Keywords

Primary biliary cirrhosis Anti-mitochondrial antibodies Antinuclear PBC-correlated antibodies Indirect immunofluorescence microscopy Solid phase methods Prognosis 

Notes

Acknowledgments

All the immunoassay kits used in this study were kindly supported by the manufacturers, namely Euroimmun, (Lübeck, Germany) and Phadia, Thermo Fisher Scientific (Uppsala, Sweden). The authors would like to thank Dr. Denis Cauchi Inglot for his essential support using the English language.

Compliance with ethical standards

Conflicts of interest

Antonio Maria Alfano, Alessandra Romito, Cristiana Marchese, Marco Battistini, Giliola Crotti, Arturo Ferrini, Cristina Mancinetti, Tilde Manetta, Giulio Mengozzi, Paola Merlach, Marco Migliardi and Maria Teresa Tambuzzo declare that they have no conflict of interest.

References

  1. 1.
    Selmi C, Bowlus CL, Gershwin ME, Coppel RL. Primary biliary cirrhosis. Lancet. 2011;377:1600–9.CrossRefPubMedGoogle Scholar
  2. 2.
    Gershwin ME, Ansari AA, Mackay IR, et al. Primary biliary cirrhosis: an orchestrated immune response against epithelial cells. Immunol Rev. 2000;174:210–25.CrossRefPubMedGoogle Scholar
  3. 3.
    Kaplan MM, Gershwin ME. Primary biliary cirrhosis. New Engl J Med. 2005;353:1261–73.CrossRefPubMedGoogle Scholar
  4. 4.
    Liu X, Invernizzi P, Lu Y, et al. Genome-wide meta-analysis identify three loci associated with primary biliary cirrhosis. Nat Genet. 2010;42:658–60.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Bogdanos DP, Vergani D. Bacteria and primary biliary cirrhosis. Clin Rev Allergy Immunol. 2009;36:30–9.CrossRefPubMedGoogle Scholar
  6. 6.
    Walden HR, Kirby JA, Yeaman SJ, Gray J, Jones DE, Palmer JM. Xenobiotic incorporation into pyruvate dehydrogenase complex can occur via the exogenous lipoylation pathway. Hepatology. 2008;48:1874–84.CrossRefPubMedGoogle Scholar
  7. 7.
    Invernizzi P. Liver auto-immunology: the paradox of autoimmunity in a tolerogenic organ. J Autoimmun. 2013;46:1–6.CrossRefPubMedGoogle Scholar
  8. 8.
    Ishibashi H, Shimoda S, Gershwin ME. The immune response to mitochondrial autoantigens. Semin Liver Dis. 2006;25:337–46.CrossRefGoogle Scholar
  9. 9.
    Walker JG, Doniach D, Roitt IM, Sherlock S. Serological tests in diagnosis of primary biliary cirrhosis. Lancet. 1965;1:827–31.CrossRefPubMedGoogle Scholar
  10. 10.
    Invernizzi P, Lleo A, Podda M. Interpreting serological tests in diagnosing autoimmune liver diseases. Semin Liver Dis. 2007;27:161–72.CrossRefPubMedGoogle Scholar
  11. 11.
    European Association for the Study of the Liever. EASL clinical pratice giudelines: management of cholestatic liver diseases. J Hepatol. 2009;51:237–67.CrossRefGoogle Scholar
  12. 12.
    Carey EJ, Ali AH, Lindor KD. Primary biliary cirrhosis. Lancet. 2015;386:1565–75.CrossRefPubMedGoogle Scholar
  13. 13.
    Mitchison HC, Bassendine MF, Hendrick A, et al. Positive antimitochondrial antibody but normal alkaline phosphase: is this primary biliary cirrosi? Hepatology. 1986;6:1279–84.CrossRefPubMedGoogle Scholar
  14. 14.
    Invernizzi P, Crosignani A, Battezzati PM, et al. Comparison of the clinical features and clinical course of antimitochondrial antibody-positive and -negative primary biliary cirrhosis. Hepatology. 1997;25:1090–5.CrossRefPubMedGoogle Scholar
  15. 15.
    Muratori L, Muratori P, Granito A, et al. The Western immunoblotting pattern of anti-mitochondrial antibodies is independent of the clinical expression of primary biliary cirrhosis. Dig Liver Dis. 2005;37:108–12.CrossRefPubMedGoogle Scholar
  16. 16.
    Nezu S, Tanaka A, Yasui H, et al. Presence of antimitochondrial autoantibodies in patients with autoimmune hepatitis. J Gastroenterol Hepatol. 2006;21:1448–54.PubMedGoogle Scholar
  17. 17.
    O’Brien C, Joshi S, Feld JJ, Guindi M, Dienes HP, Heathcote EJ. Long-term follow-up of antimitochondrial antibody-positive autoimmune hepatitis. Hepatology. 2008;48:550–6.CrossRefPubMedGoogle Scholar
  18. 18.
    Lindor KD, Gershwin ME, Poupon R, Kaplan M, Bergasa NV, Heathcote EJ. American association for study of liver diseases: primary biliary cirrhosis. Hepatology. 2009;50:291–308.CrossRefPubMedGoogle Scholar
  19. 19.
    Tomizawa M, Shinozaki F, Fugo K, et al. Anti-mitochondrial m2 antibody-positive autoimmune hepatitis. Exp Ther Med. 2015;10:1419–22.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Invernizzi P, Podda M, Battezzati PM, et al. Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis. J Hepatol. 2001;34:366–72.CrossRefPubMedGoogle Scholar
  21. 21.
    Muratori P, Muratori L, Ferrari R, et al. Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Am J Gastroenterol. 2003;98:431–7.CrossRefPubMedGoogle Scholar
  22. 22.
    Hirschfield GM, Gerhwin ME. Primary biliary Cirrhosis: one Disease with many faces. IMAJ. 2011;13:55–9.PubMedGoogle Scholar
  23. 23.
    van de Water J, Cooper A, Surh CD et al. Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis. N Engl J Med. 1989;320:1377–80.CrossRefPubMedGoogle Scholar
  24. 24.
    Liu H, Norman GL, Shums Z, et al. PBC screen: an IgG/IgA dual isotype ELISA detecting multiple mitochondrial and nuclear autoantibodies specific for primary biliary cirrhosis. J Autoimmun. 2010;35:436–42.CrossRefPubMedGoogle Scholar
  25. 25.
    Dähnrich C, Pares A, Caballeria I, et al. New ELISA for detecting primary biliary cirrhosis-specific antimitochondrial antibodies. Clin Chem. 2009;55:978–85.CrossRefPubMedGoogle Scholar
  26. 26.
    Bizzaro N, Covini G, Rosina F, et al. Overcoming a “probable” diagnosis in antimitochondrial antibody negative primary biliary cirrhosis: a study of 100 sera and review of the literature. Clin Rev Allergy Immunol. 2012;42:288–97.CrossRefPubMedGoogle Scholar
  27. 27.
    Wesierska-Gadek J, Penner E, Battezzati PM, et al. Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis. Hepatology. 2006;43:1135–44.CrossRefPubMedGoogle Scholar
  28. 28.
    Nakamura M, Kondo H, Mori T, et al. Anti-gp210 and anti-centromere antibodies are different risk factors for progression of primary biliary cirrhosis. Hepatology. 2007;45:118–27.CrossRefPubMedGoogle Scholar
  29. 29.
    Kyung-Ah K, Sook-Hyang J. The diagnosis and treatment of primary biliary cirrhosis. J Hepatol. 2011;17:173–9.Google Scholar
  30. 30.
    Corpechot C, Carrat F, Poupon R, Poupon RE. Primary biliary cirrhosis: incidence and predictive factors of cirrhosis development in ursodiol-treated patients. Gastroenterology. 2002;122:652–8.CrossRefPubMedGoogle Scholar
  31. 31.
    ter Borg PC, Schalm SW, Hansen BE, van Buuren HR. Prognosis of ursodeoxycholic Acid-treated patients with primary biliary cirrhosis. Results of a 10-yr cohort study involving 297 patients. Am J Gastroenterol. 2006;101:2044–50.CrossRefPubMedGoogle Scholar
  32. 32.
    Lammers WJ, Kowdley KV, van Buuren HR. Predicting outcome in primary biliary cirrhosis. Ann Hepatol. 2014;13(4):316–26.PubMedGoogle Scholar
  33. 33.
    Dickson ER, Grambsch PM, Fleming TR, Fisher LD, Langworthy A. Prognosis in primary biliary cirrhosis: model for decision making. Hepatology. 1989;10:1–7.CrossRefPubMedGoogle Scholar
  34. 34.
    Murtaugh PA, Dickson ER, van Dam GM, Langworthy A, Gips CH. Primary biliary cirrhosis: prediction of short-term survival based on repeated patient visits. Hepatology. 1994;20:126–34.CrossRefPubMedGoogle Scholar
  35. 35.
    Kim WR, Wiesner RH, Poterucha JJ, et al. Adaption of the Mayo primary biliary cirrhosis natural history model for application in liver transplant candidate. Liver Transpl. 2000;6:489–94.CrossRefPubMedGoogle Scholar
  36. 36.
    Lammers WJ, Hirschfield GM, Corpechot C. Development and validation of a scoring system to predict outcomes of patients with primary biliary cirrhosis receiving ursodeoxycholic acid therapy. Gastroenterology. 2015;149(7):1804–12.CrossRefPubMedGoogle Scholar
  37. 37.
    Villalta D, Sorrentino MC, Girolami E, et al. Autoantibody profiling of patients with primary biliary cirrhosis using a multiplexed line-blot assay. Clin Chim Acta. 2015;438:135–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Antonio Maria Alfano
    • 1
  • Alessandra Romito
    • 2
  • Cristiana Marchese
    • 3
  • Marco Battistini
    • 1
  • Giliola Crotti
    • 1
  • Arturo Ferrini
    • 1
  • Cristina Mancinetti
    • 1
  • Tilde Manetta
    • 4
  • Giulio Mengozzi
    • 4
  • Paola Merlach
    • 1
  • Marco Migliardi
    • 3
  • Maria Teresa Tambuzzo
    • 1
  1. 1.Clinical PathologyHospital ASL TO4CirièItaly
  2. 2.Analysis LaboratoryHospital Maria Vittoria ASL TO2TurinItaly
  3. 3.Analysis LaboratoryA.O. Ordine MaurizianoTurinItaly
  4. 4.Biochimical LaboratoryA.O.U. Città Della Salute E Della ScienzaTurinItaly

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