Skip to main content
SpringerLink
Log in

Hepatitis in the polyendocrine syndrome type 1

  • Chapter
Immunology and Liver

Part of the book series: Falk Symposium ((FASS,volume 114))

  • 124 Accesses

Abstract

Autoimmune polyendocrine syndrome type 1 (APS1) is an autosomal recessive disorder, which is caused by mutations in a single gene, called autoimmune regulator (AIRE)1,2 .The AIREgene locus is located on the long arm of chromosome 21 and codes for a transcriptional regulator, which is expressed in thymus, lymph nodes, spleen and fetal liver3. The AIREgene locus is believed to be involved in the establishment and maintenance of tolerance3. Absence of a functional AIRE protein results in a complex syndrome with mucocutaneous candidiasis and autoimmune diseases in a single patient12. Most patients with APS 1 are affected by two to six different autoimmune diseases, most of which affect endocrine glands such as parathyroids, adrenals or ovaries4. Ectodermal disease components are found with a high prevalence such as hypoplasia of the dental enamel, nail dystrophy, keratopathy, alopecia and vitiligo4. Less frequent, but severe disease components are disease manifestations which affect the gastrointestinal tract, e.g. malabsorption and hepatitis. Malabsorption may interfere with the treatment of other autoimmune diseases and cause malnutrition in severe cases5. Hepatitis may be mild. However, repeatedly patients were reported who developed lethal fulminant

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. The Finnish-German APECED Consortium. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc finger domains. Nat Genet. 1970; 17:399–403.

    Google Scholar 

  2. Nagamine K, Peterson P, Scott HS et al. Positional cloning of the APECED gene. Nature Genet. 1997;17:393–398.

    Article  PubMed  CAS  Google Scholar 

  3. Heino M, Peterson P, Kudoh J et al. Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla. Biochem Biophys Res Commun. 1999;257:821–825.

    Article  PubMed  CAS  Google Scholar 

  4. Ahonen P, Myllärniemi S, Sipilä I, Perheentupa J. Clinical variation of autoimmune polyen-docrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients.N Engl J Med. 1990;322:1829–1836.

    Article  PubMed  CAS  Google Scholar 

  5. Ekwall O, Hedstrand H, Grimelius L et al. Identification of tryptophan hydroxylase as an intestinal autoantigen. Lancet. 1998;352:255–256.

    Article  Google Scholar 

  6. Michele TM, Fleckenstein J, Sgrignoli AR, Tuluvath PJ. Chronic active hepatitis in the type I polyglandular autoimmune syndrome. J Postgrad Med. 1994;70:128–131.

    Article  CAS  Google Scholar 

  7. Obermayer-Straub P, Manns MP. The autoimmune polyglandular syndromes. Baillières Clin Gastroenterol. 1999;12:293–315.

    Article  Google Scholar 

  8. Aaltonen J, Börses P, Sandkuijl L, Perheentupa J, and Peltonen L. An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21. Nature Genet. 1994;8:83–87.

    Article  PubMed  CAS  Google Scholar 

  9. Seelig HP, Moosbrugger I, Fink T, Renz M, Genth E. The major dermatomyositis-specific Mi-2 autoantigen is a presumed helicase involved in transcriptional activation. Arthritis Rheum. 1995;38:1389–1399.

    Article  PubMed  CAS  Google Scholar 

  10. Ge Q, Nilasena DS, O’Brien CA, Frank MB, Targoff I. Molecular analysis of a major antigenic region of the 240-kD protein of Mi-2 autoantigen. J Clin Invest. 1995;96:1730–1737.

    Article  PubMed  CAS  Google Scholar 

  11. Le Douarin B, Nielsen AL, Gamier JM et al. The N-terminal part of TIF1, a putative mediator of ligand-dependent activation function (AF-2) of nuclear receptors is fused to B-raf in the oncogenic protein T18. EMBO J. 1995;14:2020–2033.

    PubMed  Google Scholar 

  12. Thenot S, Henriquet C, Rochefort H, Cavailles V. Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIFl. J Biol Chem. 1997;272:12062–12068.

    Article  PubMed  CAS  Google Scholar 

  13. Kim SS, Chen YM, O’Leary E, Witzgall R, Vidal M, Bonventre JV. A novel member of the RING finger family, KRIP-q, associates with the KRAB-A transcriptional repressor domain of zinc finger proteins. Proc Natl Acad Sci USA. 1996; 19:15299–152304.

    Article  Google Scholar 

  14. Blechschmidt K, Schweiger M, Wertz K et al. The mouse Aire gene: comparative genomic sequencing, gene organization, and expression. Genome Res. 1999;9:158–166.

    PubMed  CAS  Google Scholar 

  15. Mittaz L, Rossier C, Heino M et al. Isolation and characterization of the mouse Aire gene. Biochem Biophys Res Commun. 1999;255:483–490.

    Article  PubMed  CAS  Google Scholar 

  16. Wang CY, Shi JD, Davoodi-Semiromi A, She X. Cloning of Aire, the mouse homologue of the autoimmune regulator (AIRE) gene responsible for autoimmune polyglandular syndrome type 1 (APS 1). Genomics. 1999;55:322–326.

    Article  PubMed  CAS  Google Scholar 

  17. Björses P, Aaltonen J, Vikman A et al. Genetic homogeneity of autoimmune polyglandular disease type I.Am J Hum Genet. 1996; 59:879–886.

    PubMed  Google Scholar 

  18. Rosatelli MC, Meloni A, Meloni A et al. A common mutation in Sardinian autoimmune polyen-docrinopathy-candidiasis-ectodermal dystrophy patients. Hum Genet. 1998;103:428–434.

    Article  PubMed  CAS  Google Scholar 

  19. Pearce SHS, Cheetman T, Imrie H et al. A common and recurrent 13-bp deletion in the autoimmune regulator gene in British kindreds with autoimmune polyendocrinopathy type 1. Am J Hum Genet. 1998;63:1675–1684.

    Article  PubMed  CAS  Google Scholar 

  20. Wang C-Y, Davoodi-Semiromi A, Connor E, Shi J-D, She J-X. Characterization of mutations in patients with autoimmune polyglandular syndrome type 1 (APSl). Hum Genet. 1998;103:681–685.

    Article  PubMed  CAS  Google Scholar 

  21. Scott HS, Heino M, Peterson P et al. Common mutations in autoimmune polyendocrinopathy-can-didiasis-ectodermal dystrophy patients of different origins. Mol Endocrinol. 1998;12:1112–1119.

    Article  PubMed  CAS  Google Scholar 

  22. Betterle C, Greggio NA, Volpato M. Autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab. 1998;83:1049–1055.

    Article  PubMed  CAS  Google Scholar 

  23. Neufeld, M, Maclaren NK, Blizzard RM. Two types of autoimmune Addison’s disease associated with different polyglandular autoimmune (PGA) syndromes. Medicine. 1980;60:355–362.

    Article  Google Scholar 

  24. Li Y, Song YH, Rais N et al. Autoantibodies to the extracellular domain of the calcium sensing receptor in patients with acquired hypoparathyroidism. J Clin Invest. 1996;97:910–914.

    Article  PubMed  CAS  Google Scholar 

  25. Brown EM, Gamba G, Riccardi D et al. Cloning and characterization of an extracellular Ca2+-sensing receptor from bovine parathyroid. Nature. 1993; 366:575–580.

    Article  PubMed  CAS  Google Scholar 

  26. Ahonen P, Miettinen A, Perheentupa J. Adrenal and steroidal cell antibodies in patients with autoimmune polyglandular disease type I and risk of adrenocortical and ovarian failure. J Clin Endocrinol Metab. 1987;64:494–500.

    Article  PubMed  CAS  Google Scholar 

  27. Krohn K, Uibo R, Aavik E, Peterson P, Savilahti K. Identification by molecular cloning of an autoantigen associated with Addison’s disease as steroid 17alpha-hydroxylase. Lancet. 1992;339:770–773.

    Article  PubMed  CAS  Google Scholar 

  28. Winqvist O, Karlsson FA, Kämpe O. 21-Hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet. 1992;339:1559–1562.

    Article  PubMed  CAS  Google Scholar 

  29. Winqvist O, Gustafsson J, Rorsman F, Karlsson F, Kämpe O. Two different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome Type 1 and Addison’s disease. J Clin Invest. 1994;92:2377–2385.

    Article  Google Scholar 

  30. Uibo R, Aavik E, Peterson P, Perheentupa J, Aranko S, Pelkonen R, Krohn KJ. Autoantibodies to cytochrome P450 enzymes P450scc, P450c17, and P450c21 in autoimmune polyglandular disease types I and II and in isolated Addison’s disease. J Clin Endocrinol Metab. 1994;78:323–328.

    Article  PubMed  CAS  Google Scholar 

  31. Winqvist O, Gebre-Mehedin G, Gustafsson J et al. Identification of the main gonadal autoanti-gens in patients with adrenal insufficiency and associated ovarian failure. J Clin Endocrinol Metab. 1995;80:1717–1723.

    Article  PubMed  CAS  Google Scholar 

  32. Tsatsoulis A, Shalet SM. Antisperm antibodies in the polyglandular autoimmune (PGA) syndrome type I: response to cyclical steroid therapy. Clin Endocrinol Oxf. 1991;35:299–303.

    Article  PubMed  CAS  Google Scholar 

  33. Gorsuch AN, Spencer KM, Lister J et al. Evidence for a long prediabetic period in type I (insulin-dependent) diabetes mellitus. Lancet.1981;2:1363–1365.

    Article  PubMed  CAS  Google Scholar 

  34. Rossini AA, Greiner DL, Friedman HP, Mordes JP. Immunopathogenesis of diabetes mellitus. Diabetes Rev. 1993;1:43–75.

    Google Scholar 

  35. Baekkeskov S, Aanstoot HJ, Christgau S et al. Identification of the 64K autoantigen in insulin-dependent diabetes mellitus as the GABA-synthesizing enzyme glutamic acid decarboxylase. Nature. 1990;347:151–156.

    Article  PubMed  CAS  Google Scholar 

  36. Palmer JP. Insulin autoantibodies: their role in the pathogenesis of IDDM. Diabetes Metab. Rev. 1987;3:1005–1015.

    Article  PubMed  CAS  Google Scholar 

  37. Bruining GJ, Molenaar JL, Grobbee DE et al. Ten-year follow-up study of islet-cell antibodies and childhood diabetes mellitus. Lancet. 1989;1:1100–1103.

    Article  PubMed  CAS  Google Scholar 

  38. Greenbaum CJ, Brooks-Worrell BM, Palmer JP, Lermark A. Autoimmunity and prediction of insulin-dependent diabetes mellitus. In: Marshall H, Home PD, editors. The Diabetes Annual, vol. 8. Amsterdam: Elsevier; 1994: 21–52.

    Google Scholar 

  39. Tuomi T, Bjorses P, Falorni A et al. Antibodies to glutamic acid decarboxylase and insulin-dependent diabetes in patients with autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab. 1996;81:1488–1494.

    Article  PubMed  CAS  Google Scholar 

  40. Rorsman F, Husebye ES, Winquist O, BjE, Karlsson FA, Kämpe O. Aromatic L-aminoacid decarboxylase, a pyridoxal phosphate-dependent enzyme, is a beta-cell autoantigen. Proc Natl Acad Sci USA. 1995;92:8626–8629.

    Article  PubMed  CAS  Google Scholar 

  41. Christenson JG, Dairman W, Udenfried S. On the identity of DOPA decarboxylase and 5-hydroxytryptophan decarboxylase (immunological titration-aromatic l-aminoacid decarboxy-lase-serotonin-dopamine-norepinephrine). Proc Natl Acad Sci USA. 1972;69:343–347.

    Article  PubMed  CAS  Google Scholar 

  42. Husebye ES, Gebre-Mehedin G, Tuomi T et al. Autoantibodies against aromatic-L-amino acid decarboxylase in autoimmune polyendocrine syndrome type 1. J Clin Endocrinol Metab. 1997;82:147–150.

    Article  PubMed  CAS  Google Scholar 

  43. Bereket A, Lowenheim M, Blethen SL, Kane P, Wilson TA. Intestinal lymphangiectasia in a patient with autoimmune polyglandular disease type I and steatorrhea. J Clin Endocrinol Metab. 1994;80:933–935.

    Article  Google Scholar 

  44. Ward L, Paquette J, Seidman E et al. Severe autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy. J Clin Endocrinol Metab. 1999;84:844–851.

    Article  PubMed  CAS  Google Scholar 

  45. McGregor BC, Katz HI, Doe RP. Vitiligo and multiple glandular insufficiencies. J Am Med Assos. 1972;219:724–725.

    Article  CAS  Google Scholar 

  46. Bronstoff J. Autoantibodies in patients with vitiligo. Lancet. 1969;2:177–178.

    Article  Google Scholar 

  47. Betterle CA, Pesserico A, Bersani G. Vitiligo and autoimmune polyendocrine deficiencies with autoantibodies to melanin-producing cells. Arch. Dermatol. 1979; 115:364.

    CAS  Google Scholar 

  48. Betterle C, Caretto A, Pedini B, Rigon F, Bertoli P, Peserico A. Complement-fixing activity to melanin-producing cells preceding the onset of vitiligo in a patient with type 1 polyglandular failure [letter].Arch Dermatol. 1992;128:123–124.

    Article  PubMed  CAS  Google Scholar 

  49. Hertz KL, Gazze C, Kirkpattrick C, Katz S. Autoimmune vitiligo. N Engl J Med. 1977;297:634–637.

    Article  PubMed  CAS  Google Scholar 

  50. Sacher M, Blümel P, Thaler H, Manns M. Chronic active hepatitis associated with vitiligo, nail dystrophy, alopecia and a new variant of LKM antibodies. J Hepatol. 1990;10:364–369.

    Article  PubMed  CAS  Google Scholar 

  51. Neufeld M, Maclaren N, Blizzard R. Autoimmune polyglandular syndromes. Pediatr Ann. 1980;9:154–162.

    PubMed  CAS  Google Scholar 

  52. Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Hormone Metab Res. 1996;28:353–356.

    Article  CAS  Google Scholar 

  53. Riley WJ. Autoimmune polyglandular syndromes. Hormone Res. 1992;38(Suppl. 2):9–15.

    Article  PubMed  Google Scholar 

  54. Clemente MG, Obermayer-Straub P, Meloni A et al. Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab. 1997;82:1353–1361.

    Article  PubMed  CAS  Google Scholar 

  55. Clemente MG, Obermayer-Straub P, Meloni A et al. Cytochrome P450 1A2 as the hepatocellular autoantigen in autoimmune polyendocrine syndrome type 1. J Hepatol. 1995;23(Suppl.l):126.

    Google Scholar 

  56. Manns MP, Griffin KJ, Quattrochi L et al. Identification of cytochrome P450 IA2 as a human autoantigen. Arch Biochem Biophys. 1990;280:229–232.

    Article  PubMed  CAS  Google Scholar 

  57. Bourdi M, Larrey D, Nataf J, Bernuau J et al. Anti-liver endoplasmic reticulum antibodies are directed against human cytochrome P-450IA2. A specific marker of dihydralazine hepatitis. J Clin Invest. 1990;85:1967–1973.

    Article  PubMed  CAS  Google Scholar 

  58. Homberg JC, Abuaf N, Bernard O et al. Chronic active hepatitis associated with antiliver/kidney microsome type 1: a second type of ‘autoimmune’ hepatitis. Hepatology. 1987;7:1333–1339.

    Article  PubMed  CAS  Google Scholar 

  59. Lindgren S, Braun HB, Michel G et al. Absence of LKM-1 antibody reactivity in autoimmune and hepatitis-C-related chronic liver disease in Sweden.Swedish Internal Medicine Liver Club. Scand J Gastroenterol. 1997;32:175–178.

    Article  PubMed  CAS  Google Scholar 

  60. Czaja AJ, Manns MP, Homburger HA. Frequency and significance of antibodies to liver/kidney microsome type 1 in adults with chronic active hepatitis. Gastroenterology. 1992;103:1290–1295.

    PubMed  CAS  Google Scholar 

  61. Nebert DW, Gonzalez FJ. Cytochrome P450 genes, structure, evolution and regulation. Annu Rev Biochem. 1987;56:945–993.

    Article  PubMed  CAS  Google Scholar 

Download references

Authors
  1. P. Obermayer-Straub
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. P. Manns
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Abt. Gastroenterologie/Hepatologie Zentrum Innere Medizin, Medizinische Hochscule Hannover, Carl-Neuberg Str. 1, D-30625, Hannover, Germany

    M. P. Manns

  2. Medizinische Klinik II, Klinikum Grosshadern der LMU München, Marchioninistr. 15, D-81377, München, Germany

    G. Paumgartner

  3. Abt. Gastroenterologie Zentrum der Innere Medizin, Klinikum der Johann-Wolfgang-Goethe-Universität Frankfurt, Theodor-Stern-Kai 7, D-60596, Frankfurt, Germany

    U. Leuschner

Rights and permissions

Reprints and permissions

Copyright information

© 2000 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Obermayer-Straub, P., Manns, M.P. (2000). Hepatitis in the polyendocrine syndrome type 1. In: Manns, M.P., Paumgartner, G., Leuschner, U. (eds) Immunology and Liver. Falk Symposium, vol 114. Springer, Dordrecht. https://doi.org/10.1007/978-94-011-4000-3_10

Download citation

  • DOI: https://doi.org/10.1007/978-94-011-4000-3_10

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-5768-4

  • Online ISBN: 978-94-011-4000-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation