Gastroenterology
Volume 139, Issue 5 , Pages 1753-1761 , November 2010

α-Enolase Autoantibodies Cross-Reactive to Viral Proteins in a Mouse Model of Biliary Atresia

  • Brandy R. Lu

      Affiliations

    • Section of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children's Hospital, University of Colorado Denver School of Medicine, Aurora, Colorado
  • ,
  • Stephen M. Brindley

      Affiliations

    • Section of Allergy and Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, Colorado
  • ,
  • Rebecca M. Tucker

      Affiliations

    • Section of Allergy and Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, Colorado
  • ,
  • Cherie L. Lambert

      Affiliations

    • Section of Allergy and Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, Colorado
  • ,
  • Cara L. Mack

      Affiliations

    • Section of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children's Hospital, University of Colorado Denver School of Medicine, Aurora, Colorado
    • Section of Allergy and Clinical Immunology, University of Colorado Denver School of Medicine, Aurora, Colorado
    • Corresponding Author InformationReprint requests Address requests for reprints to: Cara L. Mack, MD, Section of Pediatric Gastroenterology, Hepatology, and Nutrition, The Children's Hospital, 13123 East 16th Ave, B290, Aurora, Colorado 80045. fax: (303) 724-7212

Received 26 January 2010 ,Accepted 9 July 2010.

References 

  1. Sokol RJ, Mack C, Narkewicz MR, et al. Pathogenesis and outcome of biliary atresia: current concepts. J Pediatr Gastroenterol Nutr. 2003;37:4–21
  2. Lykavieris P, Chardot C, Sokhn M, et al. Outcome in adulthood of biliary atresia: a study of 63 patients who survived for over 20 years with their native liver. Hepatology. 2005;41:366–371
  3. Mack CL, Tucker RM, Sokol RJ, et al. Biliary atresia is associated with CD4+ Th1 cell-mediated portal tract inflammation. Pediatr Res. 2004;56:79–87
  4. Davenport M, Gonde C, Redkar R, et al. Immunohistochemistry of the liver and biliary tress in extrahepatic biliary atresia. J Pediatr Surg. 2001;36:1017–1025
  5. Mack CL. The pathogenesis of biliary atresia: evidence for a virus-induced autoimmune disease. Semin Liver Dis. 2007;27:233–242
  6. Riepenhoff-Talty M, Schaekel K, Clark HF, et al. Group A rotavirus produce extrahepatic biliary obstruction in orally inoculated newborn mice. Pediatr Res. 1993;33:394–399
  7. Mack CL, Tucker RM, Sokol RJ, et al. Armed CD4+ Th1 effector cells and activated macrophages participate in bile duct injury in murine biliary atresia. Clin Immunol. 2005;115:200–209
  8. Shivakumar P, Campbell KM, Sabla GE, et al. Obstruction of extrahepatic bile ducts by lymphocytes is regulated by IFN-γ in experimental biliary atresia. Clin Invest. 2004;114:322–329
  9. Mack CL, Tucker RM, Lu BR, et al. Cellular and humoral autoimmunity directed at bile duct epithelia in murine biliary atresia. Hepatology. 2006;44:1231–1239
  10. Shivakumar P, Sabla G, Mohanty S, et al. Effector role of neonatal hepatic CD8+ lymphocytes in epithelial injury and autoimmunity in experimental biliary atresia. Gastroenterology. 2007;133:268–277
  11. Mack CL, Falta MF, Sullivan AK, et al. Oligoclonal expansions of CD4+ and CD8+ T cells in the target organ of patients with biliary atresia. Gastroenterology. 2007;133:278–287
  12. Hadchouel M, Hugon RN, Odievre M. Immunoglobulin deposits in the biliary remnants of extrahepatic biliary atresia: a study by immunoperoxidase staining in 128 infants. Histopathology. 1981;5:217–221
  13. Barnes BH, Tucker RM, Wehrmann F, et al. Cholangiocytes as immune modulators in rotavirus-induced murine biliary atresia. Liver Int. 2009;29:1253–1261
  14. Terrier B, Degand N, Guilpain P, et al. Alpha-enolase: a target of antibodies in infectious and autoimmune disease. Autoimmun Rev. 2007;6:176–182
  15. Shevchenko A, Tomas H, Havlis J, et al. In-gel digestion for mass spectrometric characterization of proteins and proteomes. Nat Protoc. 2006;1:2856–2860
  16. Pappin DJC, Hojrup P, Bleasby AJ. Rapid identification of proteins by peptide-mass fingerprinting. Curr Biol. 1993;3:327–332
  17. Roozendaal C, deJong MA, van den Berg AP, et al. Clinical significance of anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune liver disease. J Hepatol. 2000;32:734–741
  18. Press JL. Neonatal immunity and somatic mutation. Intern Rev Immunol. 2000;19:265–287
  19. Lundberg K, Kinloch A, Fisher BA, et al. Antibodies to citrullinated α-enolase peptide 1 are specific for rheumatoid arthritis and cross-react with bacterial enolase. Arthritis Rheum. 2008;58:3009–3019
  20. Czech-Schmidt G, Verhagen W, Szavay P, et al. Immunological gap in the infectious animal model for biliary atresia. J Surg Res. 2001;101:62–67
  21. Pancholi V. Multifunctional α-enolase: its role in disease. Cell Mol Life Sci. 2001;58:902–920
  22. Fukuda Y, Miyazawa Y, Imoto M, et al. In situ distribution of enolase isozymes in chronic liver disease. Am J Gastroenterol. 1989;84:601–605
  23. Akisawa N, Maeda T, Iwasaki S, et al. Indentification of an autoantibody against α-enolase in primary biliary cirrhosis. J Hepatol. 1997;26:845–851
  24. Orth T, Kellner R, Diekmann O, et al. Identification and characterization of autoantibodies against catalase and α-enolase in patients with primary sclerosing cholangitis. Clin Exp Immunol. 1998;112:507–515
  25. Moodie FDL, Leaker B, Cambridge G, et al. Αlpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis. Kidney Int. 1993;43:675–681
  26. Denisova E, Dowling W, LaMonica R, et al. Rotavirus capsid protein VP5* permeabilizes membrane. J Virol. 1999;73:3147–3153
  27. Dowling W, Denisova E, LaMonica R, et al. Selective membrane permeabilization by the rotavirus VP5* protein is abrogated by mutations in an internal hydrophobic domain. J Virol. 2000;74:6368–6376
  28. Dormitzer PR, Nason EB, Prasad BVV, et al. Structural rearrangements in the membrane penetration protein of a non-enveloped virus. Nature. 2004;430:1053–1058
  29. Taniguchi K, Maloy WL, Nishikawa K, et al. Identification of cross-reactive and serotype 2-specific neutralization epitopes on VP3 of human rotavirus. J Virol. 1988;62:2421–2426
  30. Tihova M, Dryden KA, Bellamy AR, et al. Localization of membrane permeabilization and receptor binding sites on the VP4 hemagglutinin of rotavirus: implications for cell entry. J Mol Biol. 2001;314:985–992
  31. Mackow ER, Barnett JW, Chan H, et al. The Rhesus rotavirus outer capsid protein VP4 functions as a hemagglutinin and is antigenically conserved when expressed by a Baculovirus recombinat. J Virol. 1989;63:1661–1668
  32. Münz C, Lünemann JD, Getts MT, et al. Antiviral immune responses: triggers of or triggered by autoimmunity?. Nat Rev Immunol. 2009;9:246–258
  33. Oldstone MBA. Molecular and cellular mechanisms, pathogenesis and treatment of insulin-dependent diabetes obtained through study of a transgenic model of molecular mimicry. Curr Top Microbiol Immunol. 2005;296:65–87
  34. Bussone G, Dib H, Dimitrov JD, et al. Identification of target antigens of self-reactive IgG in intravenous immunoglobulin preparations. Proteomics. 2009;9:1–10
  35. Robinson WH, DiGennaro C, Hueber W, et al. Autoantigen microarrays for multiplex characterization of autoantibody response. Nat Med. 2002;8:295–301
  36. Krebs P, Kurrer M, Sahin U, et al. Autoimmunity seen through the SEREX-scope. Autoimmun Rev. 2003;2:339–345

 Conflicts of interest The authors disclose no conflicts.

 Funding Supported by NIDDK, National Institutes of Health grant P30 DK048520-09 for the mass spectrometry analysis performed by the Mass Spectrometry Core Facility at University of Colorado Denver and the University of Colorado Cancer Center Proteomics Core, and NIH-NIDDK T32 DK067009-01 and The Children's Hospital Research Foundation.

PII: S0016-5085(10)01105-4

doi: 10.1053/j.gastro.2010.07.042

Gastroenterology
Volume 139, Issue 5 , Pages 1753-1761 , November 2010