Current Diabetes Reports

, Volume 5, Issue 2, pp 84–90 | Cite as

Polyendocrine autoimmunity

  • Jennifer M. Barker


Autoimmune polyendocrine disorders are characterized by the presence of more than one autoimmune endocrine disease. Study of such disorders has provided unique insight into the pathogenesis of autoimmunity and the development of tolerance in the normal individual. Autoimmune polyendocrine syndromes I and II have distinctive inheritance patterns, genetic causes, component diseases, and implications for follow-up. Care for individuals with these diseases requires monitoring for additional autoimmune disorders and aggressive treatment of identified diseases to prevent morbidity and mortality in affected individuals.


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References and Recommended Reading

  1. 1.
    Aaltonen J, Bjorses P, Sankuijl L, et al.: An autosomal locus causing autoimmune disease: autoimmune polyglandular disease type I assigned to chromosome 21. Nat Genet 1994, 8:83–87.PubMedCrossRefGoogle Scholar
  2. 2.
    An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. The Finnish-German APECED Consortium. Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy [no authors listed]. Nat Genet 1997, 17:399–403.Google Scholar
  3. 3.
    Nagamine K, Peterson P, Scott HS, et al.: Positional cloning of the APECED gene. Nat Genet 1997, 17:393–398.PubMedCrossRefGoogle Scholar
  4. 4.
    Betterle C, Greggio NA, Volpato M: Autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 1998, 83:1049–1055.PubMedCrossRefGoogle Scholar
  5. 5.
    Rostelli MC, Meloni A, Meloni A, et al.: A common mutation in Sardinian autoimmunepolyendorinopathy-candidiasisectodermal dystrophy patients. Hum Genet 1998, 103:428–434.CrossRefGoogle Scholar
  6. 6.
    Zlotogora J, Shapiro MS: Polyglandular autoimmune syndrome type I among Iranian Jews. J Med Genet 1992, 29:824–826.PubMedGoogle Scholar
  7. 7.
    Heino M, Peterson P, Kudoh J, et al.: APECED mutations in the autoimmune regulator (AIRE) gene. Hum Mutat 2001, 18:205–211.PubMedCrossRefGoogle Scholar
  8. 8.
    Bjorses P, Halonen M, Palvima JJ, et al.: Mutations in the AIRE gene: effects on sub-cellular location and transactivation function of the APECED protein. Am J Hum Genet2000, 66:378–392.PubMedCrossRefGoogle Scholar
  9. 9.
    Halonen M, Hannele K, Tuppell T, et al.: APECED-causing mutations in AIRE reveal the functional domains of the protein. Hum Mutat 2004, 23:243–257.CrossRefGoogle Scholar
  10. 10.
    Ramsey C, Winqvist O, Puhakka L, et al.: Aire deficient mice develop multiple features of APECED phenotype and show altered immune response. Hum Mol Genet 2002, 11:397–409. Report on AIRE-deficient mice with description of the altered immune response.PubMedCrossRefGoogle Scholar
  11. 11.
    Anderson MS, Venanzi ET, Klein L, et al.: Projection of an immunological self-shadow within the thymus by the aire protein. Science 2002, 298:1395–1401. Report on AIRE-deficient mice, with detailed analysis of in vivo effects of this mutation.PubMedCrossRefGoogle Scholar
  12. 12.
    Venanzi ES, Benoist C, Mathis D: Good riddance: thymocyte clonal deletion prevents autoimmunity. Curr Opin Immunol 2004, 16:197–202.PubMedCrossRefGoogle Scholar
  13. 13.
    Vafiadis P, Bettet ST, Todd JA, et al.: Insulin expression in human thymus is modulated by INS VNTR alleles at IDDM2 locus. Nat Genet 1997, 15:289–292.PubMedCrossRefGoogle Scholar
  14. 14.
    Halonen M, Eskelin P, Myhre AG, et al.: AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype. J Clin Endocrinol Metab 2002, 87:2568–2574.PubMedCrossRefGoogle Scholar
  15. 15.
    Maclaren NK, Riley WJ: Inherited susceptibility to autoimmune Addison's disease is linked to human leukocyte antigens DR3 and or DR4, except when associated with type I autoimmune polyglandular syndrome. J Clin Endocrinol Metab 1986, 62:455–459.PubMedGoogle Scholar
  16. 16.
    Gylling M, Tuomi T, Bjorses P, et al.: Beta-cell autoantibodies, human leukocyte antigen II alleles and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab 2000, 85:4434–4440.PubMedCrossRefGoogle Scholar
  17. 17.
    Ahonen P, Koskimies S, Lokki ML, et al.: The expression of autoimmune polyglandular disease type I appears associated with several HLA-A antigens but not with HLA-DR. J Clin Endocrinol Metab 1988, 66:1152–1157.PubMedCrossRefGoogle Scholar
  18. 18.
    Ahonen P, Myllarniemi S, Sipila I, Perheentupa J: Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) in a series of 68 patients. N Engl J Med 1990, 322:1829–1836.PubMedCrossRefGoogle Scholar
  19. 19.
    Betterle C, Greggio NA, Volpanto M: Clinical review: autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab 1998, 83:1049–1055.PubMedCrossRefGoogle Scholar
  20. 20.
    Perheentupa J: APS-I/APECED: the clinical disease and therapy. Endocrinol Metab Clin North Am 2002, 31:295–320. Perheentupa describes a large series of patients with APS-I that have been followed. The clinical characteristics of these patients are described and recommendations for follow-up and treatment are also given.PubMedCrossRefGoogle Scholar
  21. 21.
    Hogenauer C, Meyer RL, Netto GJ, et al.: Malabsorption due to cholecystokinin deficiency in a patient with autoimmune polyglandular syndrome type I. N Engl J Med 2001, 344:270–274.PubMedCrossRefGoogle Scholar
  22. 22.
    Skoldberg F, Portela-Gomes GM, Grimelius L: Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells. J Clin Endocrinol Metab 2003, 88:1445–1552.PubMedCrossRefGoogle Scholar
  23. 23.
    Scire G, Magliocca FM, Cianfarani S, et al.: Autoimmune polyendocrine candidiasis syndrome with associated chronic diarrhea caused by intestinal infection and pancreas insufficiency. J Pediatr Gastroenterol 1991, 13:224–227.CrossRefGoogle Scholar
  24. 24.
    Merenmies L, Tarkkanen A: Chronic bilateral keratitis in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Acta Ophthalmol Scand 2000, 78:532–534.PubMedCrossRefGoogle Scholar
  25. 25.
    Soderbergh A, Myhre AG, Ekwall O, et al.: Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type 1. J Clin Endocrinol Metab 2004, 89:557–562. Report on the association of autoantibodies and clinical disease in over 90 patients with APS-I and calculation of sensitivity and specificities of these autoantibodies.PubMedCrossRefGoogle Scholar
  26. 26.
    Fuchtenbusch M, Vogel A, Achenbach P, et al.: Lupus-like panniculitis in a patient with autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy (APECED). Exp Clin Endocrinol Diabetes 2003, 111:288–293.PubMedCrossRefGoogle Scholar
  27. 27.
    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, 84:833–852.CrossRefGoogle Scholar
  28. 28.
    Schmidt MB: Eine biglandulare Erkrankung (nebennieren und Schilddruse) bei Morbus Addisonii. Verh Dtsch Ges Pathol 1926, 21:212–221.Google Scholar
  29. 29.
    Barker JM, Eisenbarth GS: Autoimmune polyendocrine syndromes. In Type 1 Diabetes: Molecular, Cellular and Clinical Immunology. Edited by Eisenbarth GS. misc/diabetes/oxch8.html. Accessed October 29, 2004.Google Scholar
  30. 30.
    Betterle C, Lazzarotto F, Presotto F: Autoimmune polyglandular syndrome type 2: the tip of the iceberg? Clin Exp Immunol 2004, 137:225–233. A review of the clinical characteristics of APS-II, including reporting of a large group of patients with APS-II and their disease components.PubMedCrossRefGoogle Scholar
  31. 31.
    Ban Y, Davies TF, Greenberg TA, et al.: The influence of human leukocyte antigen (HLA) genes on autoimmune thyroid disease (AITD): results of studies in HLA-DR3 positive families. Clin Endocrinol 2002, 57:81–88.CrossRefGoogle Scholar
  32. 32.
    Hoffenberg EJ, McKenzie TL, Barriga KJ, et al.: A prospective study of the incidence of childhood celiac disease. J Pediatr 2003, 143:308–314.PubMedCrossRefGoogle Scholar
  33. 33.
    Redondo MJ, Fain PR, Eisenbarth GS: Genetics of type 1A diabetes. Recent Prog Horm Res 2001, 56:69–89.PubMedCrossRefGoogle Scholar
  34. 34.
    Bao F, Yu L, Babu S, et al.: One-third of HLA DQ2 homozygous patients with type 1 diabetes express celiac disease associated transglutaminase autoantibodies. J Autoimmunity 1999, 13:143–148.CrossRefGoogle Scholar
  35. 35.
    Yu L, Brewer KW, Gates S, et al.: DRB1*04 and DQ alleles: expression of 21-hydroyxlase autoantibodies and risk of progression to Addison's disease. J Clin Endocrinol Metab 1999, 84:328–335.PubMedCrossRefGoogle Scholar
  36. 36.
    Myhre AG, Undlien DE, Luvas K, et al.: Autoimmune adrenocortical failure in Norway: autoantibodies and HLA class II associations related to clinical features. J Clin Endocrinol Metab 2002, 87:618–623.PubMedCrossRefGoogle Scholar
  37. 37.
    Ota M, Katsuyama Y, Mizuki N, et al.: Trinucleotide repeat polymorphism within exon 5 of the MICA gene (MHC class I chain-related gene A): allele frequency data in the nine population groups Japanese, Northern Han, Hui, Uygur, Kazakhstan, Iranian, Saudi Arabian, Greek and Italian. Tissue Antigens 1997, 49:448–454.PubMedCrossRefGoogle Scholar
  38. 38.
    Hue S, Monteiro RC, Berrih-Aknin S, Caillat-Zucma S: Potential role of NKG2D/MHC class I-related chain A interaction in intrathymic maturation of single-positive CD8 T cells. J Immunol 2003, 171:1909–1917.PubMedGoogle Scholar
  39. 39.
    Berzina L, Shtauvere-Brameus A, Rumba I, Sanjeevi CB: Microsatellite allele A5.1 of MHC class I chain-related gene A is associated with latent autoimmune diabetes in adults in Latvia. Ann N Y Acad Sci 2002, 958:353–356.PubMedCrossRefGoogle Scholar
  40. 40.
    Park YS, Sanjeevi CB, Robles D, et al.: Additional association of intra-MHC genes, MICA and D6S273, with Addison's disease. Tissue Antigens 2002, 60:155–163.PubMedCrossRefGoogle Scholar
  41. 41.
    Rueda B, Pascual M, Lopez-Nevot MA, et al.: Association of MICA-A5.1 allele with susceptibility to celiac disease in a family study. Am J Gastroenterol 2003, 98:359–362.PubMedCrossRefGoogle Scholar
  42. 42.
    Bottini N, Muscumeci L, Alonso A, et al.: A functional variant of lymphoid tyrosine phosphatase is associated with type I diabetes. Nat Genet 2004, 36:337–338.PubMedCrossRefGoogle Scholar
  43. 43.
    Umpierrez GE, Latif KA, Murphy MB, et al.: Thyroid dysfunction in patients with type 1 diabetes: a longitudinal study. Diabetes Care 2003, 26:1181–1185. Long-term follow-up of patients with type 1 diabetes and thyroid peroxidase autoantibodies for the development of thyroid disease.PubMedCrossRefGoogle Scholar
  44. 44.
    Patel DD: Escape from tolerance in the human X-linked autoimmunity-allergic disregulation syndrome and the Scurfy mouse. J Clin Invest 2001, 107:155–157.PubMedCrossRefGoogle Scholar
  45. 45.
    Hori S, Nomura T, Sakaguchi S: Control of regulatory T cell development by the transcription factor Fox p3. Science 2003, 299:1057–1061.PubMedCrossRefGoogle Scholar
  46. 46.
    Baud O, Goulet O, Canioni D: Treatment of the immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) by allogeneic bone marrow transplantation. N Engl J Med 2001, 344:1758–1762.PubMedCrossRefGoogle Scholar
  47. 47.
    Eisenbarth GS, Gottlieb PA: Autoimmune polyendocrine syndromes. N Engl J Med 2004, 350:2068–2079. Provides an excellent summary of animal models of autoimmunity and the insight gained into human disease from the study of these models.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc. 2005

Authors and Affiliations

  • Jennifer M. Barker
    • 1
  1. 1.Barbara Davis Center for Childhood DiabetesUniversity of Colorado Health Sciences CenterDenverUSA

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