Advertisement

Autoimmune Polyglandular Syndrome Type 1

  • Pärt Peterson
Part of the Contemporary Endocrinology book series (COE)

Summary

Autoimmune polyglandular syndrome type 1 (APS1) is a monogenic autoimmune disease with organ-specific autoimmune destruction of several endocrine tissues. Most common disorders of the syndrome are chronic mucocutaneous candidiasis, hypoparathyoidism and Addison’s disease but the clinical spectrum may vary. The disease is caused by the mutations in autoimmune regulator (AIRE) gene. More than 50 mutations have been described, which are spread over the AIRE gene with two major mutation hotspots, R257X and 967-979del13bp. AIRE protein has several motifs supporting its role in transcriptional control and is highly expressed in thymic medullary epithelial cells. Analysis of AIRE deficient mice have demonstrated its role in transcriptional regulation of tissue specific antigens in medullary thymic epithelial cells, and suggested that AIRE is critical protien responsible for the maintenance of central tolerance. In agreement with mouse model, patients with APS1 have autoantibodies to multiple self-proteins. The data on cell-mediated immune responses and the reason for chronic candidiasis are still elusive. The identification of AIRE mutations and a recent finding of high titre autoantibodies to type 1 interferons should facilitate diagnosis of APS1.

Keywords

Autoimmune polyendocrinopathy autoimmune regulator autoantibodies thymus mutation. 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Esselborn VM, Landing BH, Whitaker J, Williams RR. (1956) The syndrome of familial juvenile hypoadrenocorticism, hypoparathyroidism and superficial moniliasis. J Clin Endocrinol Metab 16: 1374–1387.PubMedCrossRefGoogle Scholar
  2. 2.
    Neufeld M, Maclaren NK, Blizzard RM. (1981) Two types of autoimmune Addison’s disease associated with different polyglandular autoimmune (PGA) syndromes. Medicine 60: 355–362.PubMedGoogle Scholar
  3. 3.
    Brun JM. (1982) Juvenile autoimmune polyendocrinopathy. Horm Res 16: 308–316.PubMedGoogle Scholar
  4. 4.
    Ahonen P, Myllärniemi S, Sipilä I, Perheentupa J. (1990) Clinical variation of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)in a series of 68 patients. N Engl J Med 322: 1829–1836.PubMedCrossRefGoogle Scholar
  5. 5.
    Betterle C, Dal Pra C, Mantero F, Zanchetta R. (2002) Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev 23, 327–364.PubMedCrossRefGoogle Scholar
  6. 6.
    Nagamine K, Peterson P, Scott HS, Kudoh J, Minoshima S, Heino M, Krohn KJ, Lalioti MD, Mullis PE, Antonarakis SE, Kawasaki K, Asakawa S, Ito F and Shimizu N. (1997) Positional cloning of the APECED gene. Nat Genet 17: 393–398.PubMedCrossRefGoogle Scholar
  7. 7.
    Finnish-German APECED Consortium. (1997) An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet 17: 399–403.CrossRefGoogle Scholar
  8. 8.
    Kumar PG, Laloraya M, Wang CY, Ruan QG, Davoodi-Semiromi A, Kao KJ, She JX. (2001) The autoimmune regulator (AIRE) is a DNA-binding protein. J Biol Chem 276: 41357–41364.PubMedCrossRefGoogle Scholar
  9. 9.
    Bienz M. (2006) The PHD finger, a nuclear protein-interaction domain. Trends Biochem Sci 31: 35–40.PubMedCrossRefGoogle Scholar
  10. 10.
    Savkur RS, Burris TP. (2004) The coactivator LXXLL nuclear receptor recognition motif. J Pept Res 63: 207–212.PubMedCrossRefGoogle Scholar
  11. 11.
    Cihakova D, Trebusak K, Heino M, Fadeyev V, Tiulpakov A, Battelino T, Tar A, Halasz Z, Blumel P, Tawfik S, Krohn K, Lebl J, Peterson P. (2001) Novel AIRE mutations and P450 cytochrome autoantibodies in Central and Eastern European patients with APECED. Hum Mutat 18, 225–232.PubMedCrossRefGoogle Scholar
  12. 12.
    Sato K, Nakajima K, Imamura H, Deguchi T, Horinouchi S, Yamazaki K, Yamada E, Kanaji Y, Takano K. (2002) A novel missense mutation of AIRE gene in a patient with autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED), accompanied with progressive muscular atrophy: case report and review of the literature in Japan. Endocr J 49: 625–633.PubMedCrossRefGoogle Scholar
  13. 13.
    Pearce SH, Cheetham T, Imrie H, Vaidya B, Barnes ND, Bilous RW, Carr D, Meeran K, Shaw NJ, Smith CS, Toft AD, Williams G, Kendall-Taylor P. (1998) A common and recurrent 13-bp deletion in the autoimmune regulator gene in British kindreds with autoimmune polyendocrinopathy type 1. Am J Hum Genet 63: 1675–1684.PubMedCrossRefGoogle Scholar
  14. 14.
    Halonen M, Eskelin P, Myhre AG, Perheentupa J, Husebye ES, Kämpe O, Rorsman F, Peltonen L, Ulmanen I, Partanen J. (2002) AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype. J Clin Endocrinol Metab 87: 2568–2574.PubMedCrossRefGoogle Scholar
  15. 15.
    Heino M, Scott HS, Chen Q, Peterson P, Mäenpää U, Papasavvas MP, Mittaz L, Barras C, Rossier C, Chrousos GP, Stratakis CA, Nagamine K, Kudoh J, Shimizu N, Maclaren N, Antonarakis SE, Krohn K. (1999) Mutation analyses of North American APS-1 patients. Hum Mutat 13: 69–74.PubMedCrossRefGoogle Scholar
  16. 16.
    Kogawa K, Kudoh J, Nagafuchi S, Ohga S, Katsuta H, Ishibashi H, Harada M, Hara T, Shimizu N. (2002) Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1) associated with compound heterozygous novel AIRE gene mutations. Clin Immunol 103: 277–283.PubMedCrossRefGoogle Scholar
  17. 17.
    Ulinski T, Perrin L, Morris M, Houang M, Cabrol S, Grapin C, Chabbert-Buffet N, Bensman A, Deschenes G, Giurgea I. (2006) Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome with renal failure: impact of posttransplant immunosuppression on disease activity. J Clin Endocrinol Metab 91: 192–195.PubMedCrossRefGoogle Scholar
  18. 18.
    Meloni A, Perniola R, Faa V, Corvaglia E, Cao A, Rosatelli MC. (2002) Delineation of the molecular defects in the AIRE gene in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients from Southern Italy. J Clin Endocrinol Metab 87: 841–846.PubMedCrossRefGoogle Scholar
  19. 19.
    Björses P, Halonen M, Palvimo JJ, Kolmer M, Aaltonen J, Ellonen P, Perheentupa J, Ulmanen I, Peltonen L. (2000) Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein. Am J Hum Genet 66: 378–392.PubMedCrossRefGoogle Scholar
  20. Scott HS, Heino M, Peterson P, Mittaz L, Lalioti MD, Betterle C, Cohen A, Seri M, Lerone M, Romeo G, Collin P, Salo M, Metcalfe R, Weetman A, Papasavvas MP, Rossier C, Nagamine K, Kudoh J, Shimizu N, Krohn KJ, Antonarakis SE. (1998) Common mutations in autoimmune polyendocrinopathy-candidiasis ectodermal dystrophy patients of different origins. Mol Endocrinol 12: 1112–1119.PubMedCrossRefGoogle Scholar
  21. 21.
    Ward L, Paquette J, Seidman E, Huot C, Alvarez F, Crock P, Delvin E, Kampe O, Deal C. (1999) Severe autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in an adolescent girl with a novel AIRE mutation: response to immunosuppressive therapy. J Clin Endocrinol Metab 84: 844–852.PubMedCrossRefGoogle Scholar
  22. 22.
    Rosatelli MC, Meloni A, Meloni A, Devoto M, Cao A, Scott HS, Peterson P, Heino M, Krohn KJ, Nagamine K, Kudoh J, Shimizu N, Antonarakis SE. (1998) A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients. Hum Genet 103: 428–434.PubMedCrossRefGoogle Scholar
  23. 23.
    Wang CY, Davoodi-Semiromi A, Huang W, Connor E, Shi JD, She JX. (1998) Characterization of mutations in patients with autoimmune polyglandular syndrome type 1 (APS1). Hum Genet 103: 681–685.PubMedCrossRefGoogle Scholar
  24. 24.
    Podkrajsek KT, Bratanic N, Krzisnik C, Battelino T. (2005) Autoimmune regulator-1 messenger ribonucleic acid analysis in a novel intronic mutation and two additional novel AIRE gene mutations in a cohort of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients. J Clin Endocrinol Metab 90: 4930–4935.PubMedCrossRefGoogle Scholar
  25. 25.
    Cetani F, Barbesino G, Borsari S, Pardi E, Cianferotti L, Pinchera A, Marcocci C. (2001) A novel mutation of the autoimmune regulator gene in an Italian kindred with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, acting in a dominant fashion and strongly cosegregating with hypothyroid autoimmune thyroiditis. J Clin Endocrinol Metab 86: 4747–4752.PubMedCrossRefGoogle Scholar
  26. 26.
    Saugier-Veber P, Drouot N, Wolf LM, Kuhn JM, Frebourg T, Lefebvre H. (2001) Identification of a novel mutation in the autoimmune regulator (AIRE-1) gene in a French family with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Eur J Endocrinol 144: 347–351.PubMedCrossRefGoogle Scholar
  27. 27.
    Harris M, Kecha O, Deal C, Howlett CR, Deiss D, Tobias V, Simoneau-Roy J, Walker J. (2003) Reversible metaphyseal dysplasia, a novel bone phenotype, in two unrelated children with autoimmunepolyendocrinopathy-candidiasis-ectodermal dystrophy: clinical and molecular studies. J Clin Endocrinol Metab 88: 4576–4585.PubMedCrossRefGoogle Scholar
  28. 28.
    Söderbergh A, Rorsman F, Halonen M, Ekwall O, Björses P, Kämpe O, Husebye ES. (2000) Autoantibodies against aromatic L-amino acid decarboxylase identifies a subgroup of patients with Addison’s disease. J Clin Endocrinol Metab 85: 460–463.PubMedCrossRefGoogle Scholar
  29. 29.
    Myhre AG, Halonen M, Eskelin P, Ekwall O, Hedstrand H, Rorsman F, Kämpe O, Husebye ES. (2001) Autoimmune polyendocrine syndrome type 1 (APS I) in Norway. Clin Endocrinol (Oxf) 54: 211–217.CrossRefGoogle Scholar
  30. 30.
    Vogel A, Strassburg CP, Deiss D, Manns MP. (2003) A novel AIRE mutation in an APECED patient with candidiasis, adrenal failure, hepatitis, diabetes mellitus and osteosclerosis. Exp Clin Endocrinol Diabetes 111: 174–176.PubMedCrossRefGoogle Scholar
  31. 31.
    Ishii T, Suzuki Y, Ando N, Matsuo N, Ogata T. (2000) Novel mutations of the autoimmune regulator gene in two siblings with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab 85: 2922–2926.PubMedCrossRefGoogle Scholar
  32. 32.
    Sato U, Horikawa R, Katsumata N, Asakura Y, Kitanaka S, Tanaka T. (2004) Novel compound heterozygous AIRE mutations in a Japanese patient with APECED. J Pediatr Endocrinol Metab 17: 917–921.PubMedGoogle Scholar
  33. 33.
    Buzi F, Badolato R, Mazza C, Giliani S, Notarangelo LD, Radetti G, Plebani A, Notarangelo LD. (2003) Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome: time to review diagnostic criteria? J Clin Endocrinol Metab 88: 3146–3148.PubMedCrossRefGoogle Scholar
  34. 34.
    Gylling M, Kääriainen E, Väisanen R, Kerosuo L, Solin ML, Halme L, Saari S, Halonen M, Kämpe O, Perheentupa J, Miettinen A. (2003) The hypoparathyroidism of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protective effect of male sex. J Clin Endocrinol Metab 88: 4602–4608.PubMedCrossRefGoogle Scholar
  35. 35.
    Vaidya B, Imrie H, Geatch DR, Perros P, Ball SG, Baylis PH, Carr D, Hurel SJ, James RA, Kelly WF, Kemp EH, Young ET, Weetman AP, Kendall-Taylor P, Pearce SH. (2000). Association analysis of the cytotoxic T lymphocyte antigen-4 (CTLA-4) and autoimmune regulator-1 (AIRE-1) genes in sporadic autoimmune Addison’s disease. J Clin Endocrinol Metab 85: 688–691.PubMedCrossRefGoogle Scholar
  36. 36.
    Nithiyananthan R, Heward JM, Allahabadia A, Barnett AH, Franklyn JA, Gough SCL. (2000). A heterozygous deletion of the autoimmune regulator (AIRE1) gene, autoimmune thyroid disease, and type 1 diabetes: no evidence for association. J Clin Endocrinol Metab 85: 1320–1322.PubMedCrossRefGoogle Scholar
  37. 37.
    Meyer G, Donner H, Herwig J, Bohles H, Usadel KH, Badenhoop K. (2001) Screening for an AIRE-1 mutation in patients with Addison’s disease, type 1 diabetes, Graves’ disease and Hashimoto’s thyroiditis as well as in APECED syndrome. Clin Endocrinol (Oxf) 54: 335–338.CrossRefGoogle Scholar
  38. 38.
    Djilali-Saiah I, Renous R, Caillat-Zucman S, Debray D, Alvarez F. (2004) Linkage disequilibrium between HLA class II region and autoimmune hepatitis in pediatric patients. J Hepatol 40: 904–909.PubMedCrossRefGoogle Scholar
  39. 39.
    Torok HP, Tonenchi L, Glas J, Schiemann U, Folwaczny C. (2004) No significant association between mutations in exons 6 and 8 of the autoimmune regulator (AIRE) gene and inflammatory bowel disease. Eur J Immunogenet 31: 83–86.PubMedCrossRefGoogle Scholar
  40. 40.
    Goswami R, Gupta N, Ray D, Rani R, Tomar N, Sarin R, Vupputuri MR. (2005) Polymorphisms at +49A/G and CT60 sites in the 3’ UTR of the CTLA-4 gene and APECED-related AIRE gene mutations analysis in sporadic idiopathic hypoparathyroidism. Int J Immunogenet 32: 393–400.PubMedCrossRefGoogle Scholar
  41. 41.
    Turunen JA, Wessman M, Forsblom C, Kilpikari R, Parkkonen M, Pontynen N, Ilmarinen T, Ulmanen I, Peltonen L, Groop PH. (2006) Association analysis of the AIRE and insulin genes in Finnish type 1 diabetic patients. Immunogenetics 58:5–6.CrossRefGoogle Scholar
  42. 42.
    Tazi-Ahnini R, Cork MJ, Gawkrodger DJ, Birch MP, Wengraf D, McDonagh AJ, Messenger AG. (2002) Role of the autoimmune regulator (AIRE) gene in alopecia areata: strong association of a potentially functional AIRE polymorphism with alopecia universalis. Tissue Antigens 60: 489–495.PubMedCrossRefGoogle Scholar
  43. 43.
    Kalkhoven E. (2004) CBP and p300: HATs for different occasions. Biochem Pharmacol 68: 1145–1155.PubMedCrossRefGoogle Scholar
  44. 44.
    Akiyoshi H, Hatakeyama S, Pitkänen J, Mouri Y, Doucas V, Kudoh J, Tsurugaya K, Uchida D, Matsushima A, Oshikawa K, Nakayama KI, Shimizu N, Peterson P, Matsumoto M. (2004) Subcellular expression of autoimmune regulator is organized in a spatiotemporal manner. J Biol Chem 279: 33984–33991.PubMedCrossRefGoogle Scholar
  45. 45.
    Pitkänen J, Rebane A, Rowell J, Murumagi A, Ströbel P, Möll K, Saare M, Heikkilä J, Doucas V, Marx A, Peterson P. (2005) Cooperative activation of transcription by autoimmune regulator AIRE and CBP. Biochem Biophys Res Commun 333: 944–953.PubMedCrossRefGoogle Scholar
  46. 46.
    Uchida D, Hatakeyama S, Matsushima A, Han H, Ishido S, Hotta H, Kudoh J, Shimizu N, Doucas V, Nakayama KI, Kuroda N, Matsumoto M. (2004) AIRE functions as an E3 ubiquitin ligase. J Exp Med 199:167–172.PubMedCrossRefGoogle Scholar
  47. 47.
    Heino M, Peterson P, Kudoh J, Nagamine K, Lagerstedt A, Ovod V, Ranki A, Rantala I, Nieminen M, Tuukkanen J, Scott HS, Antonarakis SE, Shimizu N, Krohn K. (1999) Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla. Biochem Biophys Res Commun 257: 821–825.PubMedCrossRefGoogle Scholar
  48. 48.
    Zuklys S, Balciunaite G, Agarwal A, Fasler-Kan E, Palmer E, Hollander GA. (2000) Normal thymic architecture and negative selection are associated with Aire expression, the gene defective in the autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). J Immunol 165: 1976–1983.PubMedGoogle Scholar
  49. 49.
    Heino M, Peterson P, Sillanpää N, Guerin S, Wu L, Anderson G, Scott HS, Antonarakis SE, Kudoh J, Shimizu N, Jenkinson EJ, Naquet P, Krohn KJ. (2000) RNA and protein expression of the murine autoimmune regulator gene (Aire) in normal, RelB-deficient and in NOD mouse. Eur J Immunol 30:1884–1893.PubMedCrossRefGoogle Scholar
  50. 50.
    Sillanpää N, Magureanu CG, Murumägi A, Reinikainen A, West A, Manninen A, Lahti M,Ranki A, Saksela K, Krohn K, Lahesmaa R, Peterson P. (2004) Autoimmune regulator induced changes in the gene expression profile of human monocyte-dendritic cell-lineage. Mol Immunol 41: 1185–1198.PubMedCrossRefGoogle Scholar
  51. 51.
    Kogawa K, Nagafuchi S, Katsuta H, Kudoh J, Tamiya S, Sakai Y, Shimizu N, Harada M. (2002) Expression of AIRE gene in peripheral monocyte/dendritic cell lineage. Immunol Lett 80: 195–198.PubMedCrossRefGoogle Scholar
  52. 52.
    Blechschmidt K, Schweiger M, Wertz K, Poulson R, Christensen HM, Rosenthal A, Lehrach H, Yaspo ML. (1999) The mouse Aire gene: comparative genomic sequencing, gene organization, and expression. Genome Res 9:158–166.PubMedGoogle Scholar
  53. 53.
    Anderson G, Jenkinson WE, Jones T, Parnell SM, Kinsella FA, White AJ, Pongrac’z JE, Rossi SW, Jenkinson EJ. (2006) Establishment and functioning of intrathymic microenvironments. Immunol Rev 209: 10–27.PubMedCrossRefGoogle Scholar
  54. 54.
    Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, von Boehmer H, Bronson R, Dierich A, Benoist C, Mathis D. (2002) Projection of an immunological self shadow within the thymus by the aire protein. Science 298: 1395–1401.PubMedCrossRefGoogle Scholar
  55. 55.
    Kuroda N, Mitani T, Takeda N, Ishimaru N, Arakaki R, Hayashi Y, Bando Y, Izumi K, Takahashi T, Nomura T, Sakaguchi S, Ueno T, Takahama Y, Uchida D, Sun S, Kajiura F, Mouri Y, Han H, Matsushima A, Yamada G, Matsumoto M. (2005) Development of autoimmunity against transcriptionally unrepressed target antigen in the thymus of Aire-deficient mice. J Immunol 174: 1862–1870.PubMedGoogle Scholar
  56. 56.
    Kyewski B, Klein L. (2006) A central role for central tolerance. Annu Rev Immunol 24: 571–606.PubMedCrossRefGoogle Scholar
  57. 57.
    Villasenor J, Benoist C, Mathis D. (2005) AIRE and APECED: molecular insights into an autoimmune disease. Immunol Rev 204: 156–164.PubMedCrossRefGoogle Scholar
  58. 58.
    Krohn K, Uibo R, Aavik E, Peterson P, Savilahti K. (1992) Identification by molecular cloning of an autoantigen associated with Addison’s disease as steroid 17 alpha-hydroxylase. Lancet 339: 770–773.PubMedCrossRefGoogle Scholar
  59. 59.
    Winqvist O, Karlsson FA, Kämpe O. (1992) 21-Hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet 339: 1559–1562.PubMedCrossRefGoogle Scholar
  60. 60.
    Winqvist O, Gustafsson J, Rorsman F, Karlsson FA, Kämpe O. (1993) Two different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome type I and Addison’s disease. J Clin Invest 92: 2377–2385.PubMedGoogle Scholar
  61. 61.
    Uibo R, Aavik E, Peterson P, Perheentupa J, Aranko S, Pelkonen R, Krohn KJ. (1994) 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 78: 323–328.PubMedCrossRefGoogle Scholar
  62. 62.
    Björk E, Velloso LA, Kämpe O, Karlsson FA. (1994) GAD autoantibodies in IDDM, stiff-man syndrome, and autoimmune polyendocrine syndrome type I recognize different epitopes. Diabetes 43, 161–165.PubMedCrossRefGoogle Scholar
  63. 63.
    Velloso LA, Winqvist O, Gustafsson J, Kämpe O, Karlsson FA. (1994) Autoantibodies against a novel 51 kDa islet antigen and glutamate decarboxylase isoforms in autoimmune polyendocrine syndrome type I. Diabetologia 37: 61–69.PubMedCrossRefGoogle Scholar
  64. 64.
    Gylling M, Tuomi T, Björses P, Kontiainen S, Partanen J, Christie MR, Knip M, Perheentupa J, Miettinen A. (2000) ss-Cell autoantibodies, human leukocyte antigen II alleles, and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab 85: 4434–4440.PubMedCrossRefGoogle Scholar
  65. 65.
    Husebye ES, Gebre-Medhin G, Tuomi T, Perheentupa J, Landin-Olsson M, Gustafsson J, Rorsman F, Kämpe O. (1997) Autoantibodies against aromatic L-amino acid decarboxylase in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab 82: 147–150.PubMedCrossRefGoogle Scholar
  66. 66.
    Sköldberg F, Portela-Gomes GM, Grimelius L, Nilsson G, Perheentupa J, Betterle C, Husebye ES, Gustafsson J, Rönnblom A, Rorsman F, Kämpe O. (2003) Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells. J Clin Endocrinol Metab 88: 1445–1452.PubMedCrossRefGoogle Scholar
  67. 67.
    Sköldberg F, Rorsman F, Perheentupa J, Landin-Olsson M, Husebye ES, Gustafsson J, Kämpe O. (2004) Analysis of antibody reactivity against cysteine sulfinic acid decarboxylase, a pyridoxal phosphate-dependent enzyme, in endocrine autoimmune disease. J Clin Endocrinol Metab 89: 1636–1640.PubMedCrossRefGoogle Scholar
  68. 68.
    Ekwall O, Hedstrand H, Grimelius L, Haavik J, Perheentupa J, Gustafsson J, Husebye E, Kämpe O, Rorsman F. (1998) Identification of tryptophan hydroxylase as an intestinal autoantigen. Lancet 352, 279–283.PubMedCrossRefGoogle Scholar
  69. 69.
    Ekwall O, Hedstrand H, Haavik J, Perheentupa J, Betterle C, Gustafsson J, Husebye E, Rorsman F, Kämpe O. (2000) Pteridin-dependent hydroxylases as autoantigens in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab 85, 2944–2950.PubMedCrossRefGoogle Scholar
  70. 70.
    Hedstrand H, Ekwall O, Haavik J, Landgren E, Betterle C, Perheentupa J, Gustafsson J, Husebye E, Rorsman F, Kämpe O. (2000) Identification of tyrosine hydroxylase as an autoantigen in autoimmune polyendocrine syndrome type I. Biochem Biophys Res Commun 267: 456–461.PubMedCrossRefGoogle Scholar
  71. 71.
    Clemente MG, Meloni A, Obermayer-Straub P, Frau F, Manns MP, De Virgiliis S. (1998) Two cytochromes P450 are major hepatocellular autoantigens in autoimmune polyglandular syndrome type 1. Gastroenterology 114, 324–328.PubMedCrossRefGoogle Scholar
  72. 72.
    Perniola R, Falorni A, Clemente MG, Forini F, Accogli E, Lobreglio G. (2000). Organ-specific and non-organ-specific autoantibodies in children and young adults with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Eur J Endocrinol 143: 497–503.PubMedCrossRefGoogle Scholar
  73. 73.
    Hedstrand H, Ekwall O, Olsson MJ, Landgren E, Kemp EH, Weetman AP, Perheentupa J, Husebye E, Gustafsson J, Betterle C, Kämpe O, Rorsman F. (2001) The transcription factors SOX9 and SOX10 are vitiligo autoantigens in autoimmune polyendocrine syndrome type I. J Biol Chem 276: 35390–35395.PubMedCrossRefGoogle Scholar
  74. 74.
    Li Y, Song YH, Rais N, Connor E, Schatz D, Muir A, Maclaren N. (1996) Autoantibodies to the extracellular domain of the calcium sensing receptor in patients with acquired hypoparathyroidism. J Clin Invest 97: 910–914.PubMedCrossRefGoogle Scholar
  75. 75.
    Söderbergh A, Myhre AG, Ekwall O, Gebre-Medhin G, Hedstrand H, Landgren E, Miettinen A, Eskelin P, Halonen M, Tuomi T, Gustafsson J, Husebye ES, Perheentupa J, Gylling M, Manns MP, Rorsman F, Kämpe O, Nilsson T. (2004). Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab 89: 557–562.PubMedCrossRefGoogle Scholar
  76. 76.
    Peterson P, Perheentupa J, Krohn KJ. (1996) Detection of candidal antigens in autoimmune polyglandular syndrome type I. Clin Diagn Lab Immunol 3: 290–294.PubMedGoogle Scholar
  77. 77.
    Lilic D, Gravenor I, Robson N, Lammas DA, Drysdale P, Calvert JE, Cant AJ, Abinun M. (2003) Deregulated production of protective cytokines in response to Candida albicans infection in patients with chronic mucocutaneous candidiasis. Infect Immun 71: 5690–5609.PubMedCrossRefGoogle Scholar
  78. 78.
    Germain M, Gourdeau M, Hebert J. (1994) Case report: familial chronic mucocutaneous candidiasis complicated by deep candida infection. Am J Med Sci 307: 282–283.PubMedCrossRefGoogle Scholar
  79. 79.
    Matthews R, Burnie J. (1992) The role of hsp90 in fungal infection. Immunol Today 13: 345–348.PubMedCrossRefGoogle Scholar
  80. 80.
    Sediva A, Cihakova D, Lebl J. (2002) Immunological findings in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) and their family members: are heterozygotes subclinically affected? J Pediatr Endocrinol Metab 15: 1491–1496PubMedGoogle Scholar
  81. 81.
    Perniola R, Lobreglio G, Rosatelli MC, Pitotti E, Accogli E, De Rinaldis C. (2005) Immunophenotypic characterisation of peripheral blood lymphocytes in autoimmune polyglandular syndrome type 1: clinical study and review of the literature. J Pediatr Endocrinol Metab 18: 155–164.PubMedGoogle Scholar
  82. 82.
    Ryan KR, Lawson CA, Lorenzi AR, Arkwright PD, Isaacs JD, Lilic D. (2005) CD4+CD25+ T-regulatory cells are decreased in patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. J Allergy Clin Immunol 116: 1158–1159.PubMedCrossRefGoogle Scholar
  83. 83.
    Thorpe ES, Handley HE. (1929) Chronic tetany and chronic mycelial stomatitis in a child aged four and one-half years. Am J Dis Child 38: 228–238.Google Scholar
  84. 84.
    Kirkpatrick CH. (2001) Chronic mucocutaneous candidiasis. Pediatr Infect Dis J 20: 197–206.PubMedCrossRefGoogle Scholar
  85. 85.
    Perheentupa J. (2002) APS-I/APECED: the clinical disease and therapy. Endocrinol Metab Clin North Am 31: 295–320.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Pärt Peterson

There are no affiliations available

Personalised recommendations