Significance of antibodies to soluble liver antigen/liver pancreas: a large French study
Violaine Eyraud
AP-HP Hôpital Saint-Antoine, Unité d'Immunologie, Paris, France
Search for more papers by this authorOlivier Chazouilleres
AP-HP Hôpital Saint-Antoine, Service d'Hépatologie, Centre de Reference des Maladies Inflammatoires des Voies Biliaires, Paris, France
Université Pierre et Marie Curie, UFR 967 faculté de médecine, Paris, France
Search for more papers by this authorEric Ballot
AP-HP Hôpital Saint-Antoine, Unité d'Immunologie, Paris, France
Search for more papers by this authorChristophe Corpechot
AP-HP Hôpital Saint-Antoine, Service d'Hépatologie, Centre de Reference des Maladies Inflammatoires des Voies Biliaires, Paris, France
Search for more papers by this authorRaoul Poupon
AP-HP Hôpital Saint-Antoine, Service d'Hépatologie, Centre de Reference des Maladies Inflammatoires des Voies Biliaires, Paris, France
Université Pierre et Marie Curie, UFR 967 faculté de médecine, Paris, France
Search for more papers by this authorCatherine Johanet
AP-HP Hôpital Saint-Antoine, Unité d'Immunologie, Paris, France
Université Pierre et Marie Curie, UFR 967 faculté de médecine, Paris, France
Search for more papers by this authorViolaine Eyraud
AP-HP Hôpital Saint-Antoine, Unité d'Immunologie, Paris, France
Search for more papers by this authorOlivier Chazouilleres
AP-HP Hôpital Saint-Antoine, Service d'Hépatologie, Centre de Reference des Maladies Inflammatoires des Voies Biliaires, Paris, France
Université Pierre et Marie Curie, UFR 967 faculté de médecine, Paris, France
Search for more papers by this authorEric Ballot
AP-HP Hôpital Saint-Antoine, Unité d'Immunologie, Paris, France
Search for more papers by this authorChristophe Corpechot
AP-HP Hôpital Saint-Antoine, Service d'Hépatologie, Centre de Reference des Maladies Inflammatoires des Voies Biliaires, Paris, France
Search for more papers by this authorRaoul Poupon
AP-HP Hôpital Saint-Antoine, Service d'Hépatologie, Centre de Reference des Maladies Inflammatoires des Voies Biliaires, Paris, France
Université Pierre et Marie Curie, UFR 967 faculté de médecine, Paris, France
Search for more papers by this authorCatherine Johanet
AP-HP Hôpital Saint-Antoine, Unité d'Immunologie, Paris, France
Université Pierre et Marie Curie, UFR 967 faculté de médecine, Paris, France
Search for more papers by this authorAbstract
Background: Antibodies to soluble liver antigen (SLA)/liver pancreas (LP) are generally considered as highly specific diagnostic markers of type 1 auto-immune hepatitis (AIH-1), and are particularly useful in patients without conventional antibodies. However, the presence of anti-SLA/LP in type 2 auto-immune hepatitis (AIH-2), primary sclerosing cholangitis (PSC) and hepatitis C has recently been reported. The aim was thus to describe the characteristics of anti-SLA/LP-positive patients in the largest series reported to date.
Methods: Sera were selected from the period between 1998 and 2005, based on the presence of antibodies to SLA/LP detected by two methods. The clinical status of patients was determined from their medical records.
Results: Eighty-one anti-SLA/LP-positive patients with available clinical data were included: 89% (72/81) had a diagnosis of AIH-1, including 10 (12%) associated with cholestatic diseases (primary biliary cirrhosis in seven cases and PSC in three cases). Six patients (7%) suffered from another liver disease: hepatitis C (n=3) and drug-induced hepatitis (n=3). No specific diagnosis was made in three patients.
Conclusions: Antibodies to SLA/LP are of a major diagnostic value for AIH-1, including paediatric forms and overlap syndromes with cholestatic diseases, but are not found in association with anti-liver/kidney/microsome type 1 or antibodies to liver cytosol type 1. They are rarely present in other liver diseases such as hepatitis C and drug-induced hepatitis.
References
- 1 Manns MP, Strassburg CP. Autoimmune hepatitis: clinical challenges. Gastroenterology 2001; 120: 1502–17.
- 2 Obermayer-Straub P, Strassburg CP, Manns MP. Autoimmune hepatitis. J Hepatol 2000; 32: 181–97.
- 3 Czaja AJ, Bianchi AC, Krawitt EL, et al. Treatment challenges and investigational opportunities in autoimmune hepatitis. Hepatology 2005; 41: 207–15.
- 4 Johnson PJ, Mcfarlane IG. Meeting report: International Autoimmune Hepatitis Group. Hepatology 1993; 18: 998–1005.
- 5 Alvarez F, Berg PA, Bianchi FB, et al. International Autoimmune Hepatitis Group Report: review of criteria for diagnosis of autoimmune hepatitis. J Hepatol 1999; 31: 929–38.
- 6 Czaja J, Homburger H. Autoantibodies in liver disease. Gastroenterology 2001; 120: 239–49.
- 7 Vergani D, Alvarez F, Bianchi FB, et al. Liver autoimmune serology: a consensus statement from the committee for autoimmune serology of the International Autoimmune Hepatitis Group. J Hepatol 2004; 41: 677–83.
- 8 Manns MP, Gerken G, Kryiatsoulis A, et al. Characterization of a new subgroup of autoimmune chronic active hepatitis by autoantibodies against a soluble liver antigen. Lancet 1987; 1: 292–4.
- 9 Czaja AJ, Carpenter HA, Manns MP. Antibodies to soluble liver antigen, P450IID6, and mitochondrial complexes in chronic hepatitis. Gastroenterology 1993; 105: 1522–8.
- 10 Lohse AW, Gerken G, Mohr H, et al. Relation between autoimmune liver disease and viral hepatitis: clinical and serological characteristics in 859 patients. J Gastroenterol 1995; 33: 527–33.
- 11 Nishioka M, Morshed SA, Parveen S, et al. Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 in Japanese patients with chronic hepatitis. J Gastroenterol Hepatol 1997; 12: 862–8.
- 12 Kanzler S, Weidemann C, Gerken G, et al. Clinical significance of autoantibodies to soluble liver antigen in autoimmune hepatitis. J Hepatol 1999; 31: 635–40.
- 13 Ballot E, Homberg JC, Johanet C. Antibodies to soluble liver antigen: an additional marker in type 1 auto-immune hepatitis. J Hepatol 2000; 33: 208–15.
- 14 Wies I, Brunner S, Henninger J, et al. Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis. Lancet 2000; 355: 1510–15.
- 15 Baeres M, Herkel J, Czaja AJ, et al. Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics. Gut 2002; 51: 259–64.
- 16 Miyakawa H, Kawashima Y, Kitazawa E, et al. Low frequency of anti-SLA/LP autoantibodies in Japanese adult patients with autoimmune liver diseases: analysis with recombinant antigen assay. J Autoimmun 2003; 21: 77–82.
- 17 Torres-Collado AX, Czaja AJ, Gelpi C. Anti t-RNP(ser)sec/SLA/LP autoantibodies. Comparative study using in-house ELISA with a recombinant 48.8 kDa protein, immunoblot, and analysis of immunoprecipitated RNAs. Liver Int 2005; 25: 410–9.
- 18 Araiso Y, Palioura S, Ishitani R, et al. Structural insights into RNA-dependent eukaryal and archaeal selenocysteine formation. Nucleic Acids Res 2008; 36: 1187–99.
- 19 Czaja AJ, Shums Z, Norman GL. Frequency and significance of antibodies to soluble liver antigen/liver pancreas in variant autoimmune hepatitis. Autoimmunity 2002; 35: 475–83.
- 20 Czaja AJ, Shums Z, Norman GL. Nonstandard antibodies as prognostic markers in autoimmune hepatitis. Autoimmunity 2004; 37: 195–201.
- 21 Ma Y, Okamoto M, Thomas MG, et al. Antibodies to conformational epitopes of soluble liver antigen define a severe form of autoimmune liver disease. Hepatology 2002; 35: 658–64.
- 22 Vitozzi S, Djilali-Saiah I, Lapierre P, et al. Anti-soluble liver antigen/liver pancreas (SLA/LP) antibodies in pediatric patients with autoimmune hepatitis. Autoimmunity 2002; 35: 485–92.
- 23 Vitozzi S, Lapierre P, Djilali-Saiah I, et al. Anti-soluble liver antigen (SLA) antibodies in chronic HCV infection. Autoimmunity 2004; 37: 217–22.
- 24 Chazouillères O, Wendum D, Serfaty L, et al. Primary biliary cirrhosis–autoimmune hepatitis overlap syndrome: clinical features and response to therapy. Hepatology 1998; 28: 296–301.
- 25 Ben-Ari Z, Czaja AJ. Autoimmune hepatitis and its variant syndromes. Gut 2001; 49: 589–94.
- 26 Bedossa P, Poynard T for the Metavir Cooperative Study Group. An algorithm for the grading of activity in chronic hepatitis C. Hepatology 1996; 24: 289–93.
- 27 Grüber R, Felber E, Pape GR, et al. Detection of antibodies against M2, LKM-1, and SLA in liver diseases by standardized uniform ELISA-techniques. J Clin Lab Anal 1994; 8: 284–92.
- 28 De Duve C, Pressman BC, Gianetto R, et al. Tissue fractionation studies – 6. Intracellular distribution patterns of enzymes in rat liver tissue. Biochem J 1955; 60: 604–17.
- 29 Laemmli UK. Cleavage of structural protein during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680–5.
- 30 Towbin H, Staehelin T, Gordon J. Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci USA 1979; 76: 4350–4.
- 31 Lohse AW, Hennes E. Diagnostic criteria for autoimmune hepatitis. Hepatol Res 2007; 37: S509.
- 32 Granito A, Muratori P, Muratori L, et al. Antibodies to SS-A/Ro-52kD and centromere in autoimmune liver disease: a clue to diagnosis and prognosis of primary biliary cirrhosis. Aliment Pharmacol Ther 2007; 26: 831–8.
- 33 Rigopoulou EI, Mytilinaiou M, Romanidou O, et al. Autoimmune hepatitis-specific antibodies against soluble liver antigen and liver cytosol type 1 in patients with chronic viral hepatitis. J Autoimmune Dis 2007; 4: 2.
- 34 Liu ZX, Kaplowitz N. Immune-mediated drug-induced liver disease. Clin Liver Dis 2002; 6: 755–74.
- 35 Clemente MG, De Virgiliis S. Autoantigen characterization in liver/kidney microsome positive hepatitis. Digest Liver Dis 2000; 32: 39–45.
- 36 Scully LJ, Clarke D, Barr RJ. Diclofenac induced hepatitis. 3 cases with features of autoimmune chronic active hepatitis. Dig Dis Sci 1993; 38: 744–51.
- 37 Alla V, Abraham J, Siddiqui J, et al. Autoimmune hepatitis triggered by statins. J Clin Gastroenterol 2006; 40: 757–61.
- 38 Harel M, Shoenfeld Y. Predicting and preventing autoimmunity, myth or reality? Ann NY Acad Sci 2006; 1069: 322–45.
- 39 Metcalf JV, Mitchison HC, Palmer JM, et al. Natural history of early primary biliary cirrhosis. Lancet 1996; 348: 1399–402.
- 40 Czaja AJ, Donaldson PT, Lohse AW. Antibodies to soluble liver antigen/liver pancreas and HLA risk factors for type 1 autoimmune hepatitis. Am J Gastroenterol 2002; 97: 413–19.
- 41 Duclos-Vallée JC, Sebagh M, Rifai K, et al. A 10 year follow up study of patients transplanted for autoimmune hepatitis: histological recurrence precedes clinical and biochemical recurrence. Gut 2003; 52: 893–7.
Citing Literature
