nach oben

Journal of Clinical Immunology

Erschienen in:

01.07.2015 | CME Review

Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy

verfasst von: Kai Kisand, Pärt Peterson

Erschienen in: Journal of Clinical Immunology | Ausgabe 5/2015

Einloggen, um Zugang zu erhalten

Abstract

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED) is an autosomal recessive disease caused by mutations in the autoimmune regulator (AIRE) gene. This review focuses on the clinical and immunological features of APECED, summarizes the current knowledge on the function of AIRE and discusses the importance of autoantibodies in disease diagnosis and prognosis. Additionally, we review the outcome of recent immunomodulatory treatments in APECED patients.

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;322:1829–36.PubMed

Perheentupa J. APS-I/APECED: the clinical disease and therapy. Endocrinol Metab Clin N Am. 2002;31:295–320.

Nagamine K, Peterson P, Scott HS, Kudoh J, Minoshima S, Heino M, et al. Positional cloning of the APECED gene. Nat Genet. 1997;17:393–8.PubMed

Consortium F-GA. An autoimmune disease, APECED, caused by mutations in a novel gene featuring two PHD-type zinc-finger domains. Nat Genet. 1997;17:399–403.

Zlotogora J, Shapiro MS. Polyglandular autoimmune syndrome type I among Iranian Jews. J Med Genet. 1992;29:824–6.PubMedCentralPubMed

Rosatelli MC, Meloni A, Meloni A, Devoto M, Cao A, Scott HS, et al. A common mutation in Sardinian autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients. Hum Genet. 1998;103:428–34.PubMed

Perheentupa J. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab. 2006;91:2843–50.PubMed

Podkrajsek KT, Bratanic N, Krzisnik C, Battelino T. 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. 2005;90:4930–5.PubMed

Myhre AG, Halonen M, Eskelin P, Ekwall O, Hedstrand H, Rorsman F, et al. Autoimmune polyendocrine syndrome type 1 (APS I) in Norway. Clin Endocrinol (Oxf). 2001;54:211–7.

10.

Stolarski B, Pronicka E, Korniszewski L, Pollak A, Kostrzewa G, Rowinska E, et al. Molecular background of polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome in a Polish population: novel AIRE mutations and an estimate of disease prevalence. Clin Genet. 2006;70:348–54.PubMed

11.

Husebye ES, Perheentupa J, Rautemaa R, Kampe O. Clinical manifestations and management of patients with autoimmune polyendocrine syndrome type I. J Intern Med. 2009;265:514–29.PubMed

12.

Peterson P, Peltonen L. Autoimmune polyendocrinopathy syndrome type 1 (APS1) and AIRE gene: new views on molecular basis of autoimmunity. J Autoimmun. 2005;25(Suppl):49–55.PubMed

13.

Cetani F, Barbesino G, Borsari S, Pardi E, Cianferotti L, Pinchera A, et al. 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. 2001;86:4747–52.PubMed

14.

Boe AS, Knappskog PM, Myhre AG, Sorheim JI, Husebye ES. Mutational analysis of the autoimmune regulator (AIRE) gene in sporadic autoimmune Addison’s disease can reveal patients with unidentified autoimmune polyendocrine syndrome type I. Eur J Endocrinol. 2002;146:519–22.PubMed

15.

Cervato S, Morlin L, Albergoni MP, Masiero S, Greggio N, Meossi C, et al. AIRE gene mutations and autoantibodies to interferon omega in patients with chronic hypoparathyroidism without APECED. Clin Endocrinol (Oxf). 2010;73:630–6.

16.

Meager A, Visvalingam K, Peterson P, Moll K, Murumagi A, Krohn K, et al. Anti-interferon autoantibodies in autoimmune polyendocrinopathy syndrome type 1. PLoS Med. 2006;3:e289.PubMedCentralPubMed

17.

Meloni A, Furcas M, Cetani F, Marcocci C, Falorni A, Perniola R, et al. Autoantibodies against type I interferons as an additional diagnostic criterion for autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab. 2008;93:4389–97.PubMed

18.

Toth B, Wolff AS, Halasz Z, Tar A, Szuts P, Ilyes I, et al. Novel sequence variation of AIRE and detection of interferon-omega antibodies in early infancy. Clin Endocrinol (Oxf). 2010;72:641–7.

19.

Wolff AS, Erichsen MM, Meager A, Magitta NF, Myhre AG, Bollerslev J, et al. Autoimmune polyendocrine syndrome type 1 in Norway: phenotypic variation, autoantibodies, and novel mutations in the autoimmune regulator gene. J Clin Endocrinol Metab. 2007;92:595–603.PubMed

20.

Zhang L, Barker JM, Babu S, Su M, Stenerson M, Cheng M, et al. A robust immunoassay for anti-interferon autoantibodies that is highly specific for patients with autoimmune polyglandular syndrome type 1. Clin Immunol. 2007;125:131–7.PubMedCentralPubMed

21.

Husebye ES, Anderson MS. Autoimmune polyendocrine syndromes: clues to type 1 diabetes pathogenesis. Immunity. 2011;32:479–87.

22.

Wolff AS, Sarkadi AK, Marodi L, Karner J, Orlova E, Oftedal BE, et al. Anti-cytokine autoantibodies preceding onset of autoimmune polyendocrine syndrome type I features in early childhood. J Clin Immunol. 2013;33:1341–8.PubMed

23.

Meloni A, Willcox N, Meager A, Atzeni M, Wolff AS, Husebye ES, et al. Autoimmune polyendocrine syndrome type 1: an extensive longitudinal study in Sardinian patients. J Clin Endocrinol Metab. 2012;97:1114–24.PubMed

24.

Meager A, Vincent A, Newsom-Davis J, Willcox N. Spontaneous neutralising antibodies to interferon--alpha and interleukin-12 in thymoma-associated autoimmune disease. Lancet. 1997;350:1596–7.PubMed

25.

Rice GI, Forte GM, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, et al. Assessment of interferon-related biomarkers in Aicardi-Goutieres syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case–control study. Lancet Neurol. 2013;12:1159–69.PubMedCentralPubMed

26.

Meager A, Wadhwa M, Dilger P, Bird C, Thorpe R, Newsom-Davis J, et al. Anti-cytokine autoantibodies in autoimmunity: preponderance of neutralizing autoantibodies against interferon-alpha, interferon-omega and interleukin-12 in patients with thymoma and/or myasthenia gravis. Clin Exp Immunol. 2003;132:128–36.PubMedCentralPubMed

27.

Kluger N, Kataja J, Aho H, Ronn AM, Krohn K, Ranki A. Kidney involvement in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy in a Finnish cohort. Nephrol Dial Transplant. 2014;29:1750–7.PubMed

28.

Oftedal BE, Wolff AS, Bratland E, Kampe O, Perheentupa J, Myhre AG, et al. Radioimmunoassay for autoantibodies against interferon omega; its use in the diagnosis of autoimmune polyendocrine syndrome type I. Clin Immunol. 2008;129:163–9.PubMed

29.

Puel A, Doffinger R, Natividad A, Chrabieh M, Barcenas-Morales G, Picard C, et al. Autoantibodies against IL-17A, IL-17F, and IL-22 in patients with chronic mucocutaneous candidiasis and autoimmune polyendocrine syndrome type I. J Exp Med. 2010;207:291–7.PubMedCentralPubMed

30.

Karner J, Meager A, Laan M, Maslovskaja J, Pihlap M, Remm A, et al. Anti-cytokine autoantibodies suggest pathogenetic links with autoimmune regulator deficiency in humans and mice. Clin Exp Immunol. 2013;171:263–72.PubMedCentralPubMed

31.

Burbelo PD, Browne SK, Sampaio EP, Giaccone G, Zaman R, Kristosturyan E, et al. Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia. Blood. 2010;116:4848–58.PubMedCentralPubMed

32.

Kisand K, Link M, Wolff AS, Meager A, Tserel L, Org T, et al. Interferon autoantibodies associated with AIRE deficiency decrease the expression of IFN-stimulated genes. Blood. 2008;112:2657–66.PubMedCentralPubMed

33.

Breivik L, Oftedal BE, Boe Wolff AS, Bratland E, Orlova EM, Husebye ES. A novel cell-based assay for measuring neutralizing autoantibodies against type I interferons in patients with autoimmune polyendocrine syndrome type 1. Clin Immunol. 2014;153:220–7.PubMed

34.

Arstila TP, Jarva H. Human APECED; a sick thymus syndrome? Front Immunol. 2013;4:313.PubMedCentralPubMed

35.

Heino M, Peterson P, Kudoh J, Nagamine K, Lagerstedt A, Ovod V, et al. Autoimmune regulator is expressed in the cells regulating immune tolerance in thymus medulla. Biochem Biophys Res Commun. 1999;257:821–5.PubMed

36.

Gardner JM, Devoss JJ, Friedman RS, Wong DJ, Tan YX, Zhou X, et al. Deletional tolerance mediated by extrathymic Aire-expressing cells. Science. 2008;321:843–7.PubMedCentralPubMed

37.

Poliani PL, Kisand K, Marrella V, Ravanini M, Notarangelo LD, Villa A, et al. Human peripheral lymphoid tissues contain autoimmune regulator-expressing dendritic cells. Am J Pathol. 2010;176:1104–12.PubMedCentralPubMed

38.

Bjorses P, Halonen M, Palvimo JJ, Kolmer M, Aaltonen J, Ellonen P, et al. Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein. Am J Hum Genet. 2000;66:378–92.PubMedCentralPubMed

39.

Bernardi R, Pandolfi PP. Structure, dynamics and functions of promyelocytic leukaemia nuclear bodies. Nat Rev Mol Cell Biol. 2007;8:1006–16.PubMed

40.

Peterson P, Org T, Rebane A. Transcriptional regulation by AIRE: molecular mechanisms of central tolerance. Nat Rev Immunol. 2008;8:948–57.PubMedCentralPubMed

41.

Ferguson BJ, Alexander C, Rossi SW, Liiv I, Rebane A, Worth CL, et al. AIRE’s CARD revealed, a new structure for central tolerance provokes transcriptional plasticity. J Biol Chem. 2008;283:1723–31.PubMed

42.

Kyewski B, Derbinski J. Self-representation in the thymus: an extended view. Nat Rev Immunol. 2004;4:688–98.PubMed

43.

Liston A, Lesage S, Wilson J, Peltonen L, Goodnow CC. Aire regulates negative selection of organ-specific T cells. Nat Immunol. 2003;4:350–4.PubMed

44.

Anderson MS, Venanzi ES, Klein L, Chen Z, Berzins SP, Turley SJ, et al. Projection of an immunological self shadow within the thymus by the aire protein. Science. 2002;298:1395–401.PubMed

45.

Malchow S, Leventhal DS, Nishi S, Fischer BI, Shen L, Paner GP, et al. Aire-dependent thymic development of tumor-associated regulatory T cells. Science. 2013;339:1219–24.PubMedCentralPubMed

46.

Yang S, Fujikado N, Kolodin D, Benoist C, Mathis D. Immune tolerance. Regulatory T cells generated early in life play a distinct role in maintaining self-tolerance. Science. 2015;348:589–94.PubMed

47.

Gaetani M, Matafora V, Saare M, Spiliotopoulos D, Mollica L, Quilici G, et al. AIRE-PHD fingers are structural hubs to maintain the integrity of chromatin-associated interactome. Nucleic Acids Res. 2012;40:11756–68.PubMedCentralPubMed

48.

Abramson J, Giraud M, Benoist C, Mathis D. Aire’s partners in the molecular control of immunological tolerance. Cell. 2010;140:123–35.PubMed

49.

Org T, Chignola F, Hetenyi C, Gaetani M, Rebane A, Liiv I, et al. The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression. EMBO Rep. 2008;9:370–6.PubMedCentralPubMed

50.

Koh AS, Kuo AJ, Park SY, Cheung P, Abramson J, Bua D, et al. Aire employs a histone-binding module to mediate immunological tolerance, linking chromatin regulation with organ-specific autoimmunity. Proc Natl Acad Sci U S A. 2008;105:15878–83.PubMedCentralPubMed

51.

Chignola F, Gaetani M, Rebane A, Org T, Mollica L, Zucchelli C, et al. The solution structure of the first PHD finger of autoimmune regulator in complex with non-modified histone H3 tail reveals the antagonistic role of H3R2 methylation. Nucleic Acids Res. 2009;37:2951–61.PubMedCentralPubMed

52.

Pitkanen J, Rebane A, Rowell J, Murumagi A, Strobel P, Moll K, et al. Cooperative activation of transcription by autoimmune regulator AIRE and CBP. Biochem Biophys Res Commun. 2005;333:944–53.PubMed

53.

Zumer K, Plemenitas A, Saksela K, Peterlin BM. Patient mutation in AIRE disrupts P-TEFb binding and target gene transcription. Nucleic Acids Res. 2011;39:7908–19.PubMedCentralPubMed

54.

Giraud M, Yoshida H, Abramson J, Rahl PB, Young RA, Mathis D, et al. Aire unleashes stalled RNA polymerase to induce ectopic gene expression in thymic epithelial cells. Proc Natl Acad Sci U S A. 2012;109:535–40.PubMedCentralPubMed

55.

Giraud M, Jmari N, Du L, Carallis F, Nieland TJ, Perez-Campo FM, et al. An RNAi screen for Aire cofactors reveals a role for Hnrnpl in polymerase release and Aire-activated ectopic transcription. Proc Natl Acad Sci U S A. 2014;111:1491–6.PubMedCentralPubMed

56.

Chuprin A, Avin A, Goldfarb Y, Herzig Y, Levi B, Jacob A, et al. The deacetylase Sirt1 is an essential regulator of Aire-mediated induction of central immunological tolerance. Nat Immunol. 2015;16:737–45.

57.

Wang X, Laan M, Bichele R, Kisand K, Scott HS, Peterson P. Post-Aire maturation of thymic medullary epithelial cells involves selective expression of keratinocyte-specific autoantigens. Front Immunol. 2012;3:1–16.

58.

Matsumoto M. Contrasting models for the roles of Aire in the differentiation program of epithelial cells in the thymic medulla. Eur J Immunol. 2011;41:12–7.PubMed

59.

Matsumoto M, Nishikawa Y, Nishijima H, Morimoto J, Matsumoto M, Mouri Y. Which model better fits the role of aire in the establishment of self-tolerance: the transcription model or the maturation model? Front Immunol. 2013;4:210.PubMedCentralPubMed

60.

Laan M, Peterson P. The many faces of aire in central tolerance. Front Immunol. 2013;4:326.PubMedCentralPubMed

61.

Kisand K, Peterson P, Laan M. Lymphopenia-induced proliferation in aire-deficient mice helps to explain their autoimmunity and differences from human patients. Front Immunol. 2014;5:51.PubMedCentralPubMed

62.

Nishikawa Y, Nishijima H, Matsumoto M, Morimoto J, Hirota F, Takahashi S, et al. Temporal lineage tracing of Aire-expressing cells reveals a requirement for Aire in their maturation program. J Immunol. 2014;192:2585–92.PubMed

63.

Podkrajsek KT, Milenkovic T, Odink RJ, der Grinten HL C-v, Bratanic N, Hovnik T, et al. Detection of a complete autoimmune regulator gene deletion and two additional novel mutations in a cohort of patients with atypical phenotypic variants of autoimmune polyglandular syndrome type 1. Eur J Endocrinol. 2008;159:633–9.PubMed

64.

Boe Wolff AS, Oftedal B, Johansson S, Bruland O, Lovas K, Meager A, et al. AIRE variations in Addison’s disease and autoimmune polyendocrine syndromes (APS): partial gene deletions contribute to APS I. Genes Immun. 2008;9:130–6.PubMed

65.

Peterson P, Pitkanen J, Sillanpaa N, Krohn K. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a model disease to study molecular aspects of endocrine autoimmunity. Clin Exp Immunol. 2004;135:348–57.PubMedCentralPubMed

66.

Ilmarinen T, Eskelin P, Halonen M, Ruppell T, Kilpikari R, Torres GD, et al. Functional analysis of SAND mutations in AIRE supports dominant inheritance of the G228W mutation. Hum Mutat. 2005;26:322–31.PubMed

67.

Su MA, Giang K, Zumer K, Jiang H, Oven I, Rinn JL, et al. Mechanisms of an autoimmunity syndrome in mice caused by a dominant mutation in Aire. J Clin Invest. 2008;118:1712–26.PubMedCentralPubMed

68.

Halonen M, Eskelin P, Myhre AG, Perheentupa J, Husebye ES, Kampe O, et al. AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype. J Clin Endocrinol Metab. 2002;87:2568–74.PubMed

69.

Kisand K, Boe Wolff AS, Podkrajsek KT, Tserel L, Link M, Kisand KV, et al. Chronic mucocutaneous candidiasis in APECED or thymoma patients correlates with autoimmunity to Th17-associated cytokines. J Exp Med. 2010;207:299–308.PubMedCentralPubMed

70.

Kisand K, Lilic D, Casanova JL, Peterson P, Meager A, Willcox N. Mucocutaneous candidiasis and autoimmunity against cytokines in APECED and thymoma patients: clinical and pathogenetic implications. Eur J Immunol. 2011;41:1517–27.PubMed

71.

Betterle C, Greggio NA, Volpato M. Clinical review 93: autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab. 1998;83:1049–55.PubMed

72.

Collins SM, Dominguez M, Ilmarinen T, Costigan C, Irvine AD. Dermatological manifestations of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. Br J Dermatol. 2006;154:1088–93.PubMed

73.

Rautemaa R, Hietanen J, Niissalo S, Pirinen S, Perheentupa J. Oral and oesophageal squamous cell carcinoma--a complication or component of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED, APS-I). Oral Oncol. 2007;43:607–13.PubMed

74.

Liang SC, Tan XY, Luxenberg DP, Karim R, Dunussi-Joannopoulos K, Collins M, et al. Interleukin (IL)-22 and IL-17 are coexpressed by Th17 cells and cooperatively enhance expression of antimicrobial peptides. J Exp Med. 2006;203:2271–9.PubMedCentralPubMed

75.

Conti HR, Baker O, Freeman AF, Jang WS, Holland SM, Li RA, et al. New mechanism of oral immunity to mucosal candidiasis in hyper-IgE syndrome. Mucosal Immunol. 2011;4:448–55.PubMedCentralPubMed

76.

Sonnenberg GF, Fouser LA, Artis D. Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22. Nat Immunol. 2011;12:383–90.PubMed

77.

Eyerich S, Wagener J, Wenzel V, Scarponi C, Pennino D, Albanesi C, et al. IL-22 and TNF-alpha represent a key cytokine combination for epidermal integrity during infection with Candida albicans. Eur J Immunol. 2011;41:1894–901.PubMed

78.

Liu L, Okada S, Kong XF, Kreins AY, Cypowyj S, Abhyankar A, et al. Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis. J Exp Med. 2011;208:1635–48.PubMedCentralPubMed

79.

Eyerich K, Foerster S, Rombold S, Seidl HP, Behrendt H, Hofmann H, et al. Patients with chronic mucocutaneous candidiasis exhibit reduced production of Th17-associated cytokines IL-17 and IL-22. J Invest Dermatol. 2008;128:2640–5.PubMed

80.

Ahlgren KM, Moretti S, Lundgren BA, Karlsson I, Ahlin E, Norling A, et al. Increased IL-17A secretion in response to Candida albicans in autoimmune polyendocrine syndrome type 1 and its animal model. Eur J Immunol. 2011;41:235–45.PubMed

81.

Ng WF, von Delwig A, Carmichael AJ, Arkwright PD, Abinun M, Cant AJ, et al. Impaired T(H)17 responses in patients with chronic mucocutaneous candidiasis with and without autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Allergy Clin Immunol. 2010;126:1006–15.PubMed

82.

Laakso SM, Kekalainen E, Heikkila N, Mannerstrom H, Kisand K, Peterson P, et al. In vivo analysis of helper T cell responses in patients with autoimmune polyendocrinopathy - candidiasis - ectodermal dystrophy provides evidence in support of an IL-22 defect. Autoimmunity. 2014;47:556–62.PubMed

83.

Sarkadi AK, Tasko S, Csorba G, Toth B, Erdos M, Marodi L. Autoantibodies to IL-17A may be correlated with the severity of mucocutaneous candidiasis in APECED patients. J Clin Immunol. 2014;34:181–93.PubMed

84.

Mazza C, Buzi F, Ortolani F, Vitali A, Notarangelo LD, Weber G, et al. Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome. Clin Immunol. 2011;139:6–11.PubMed

85.

Betterle C, Zanchetta R. Update on autoimmune polyendocrine syndromes (APS). Acta Biomed. 2003;74:9–33.PubMed

86.

Orlova EM, Bukina AM, Kuznetsova ES, Kareva MA, Zakharova EU, Peterkova VA, et al. Autoimmune polyglandular syndrome type 1 in Russian patients: clinical variants and autoimmune regulator mutations. Horm Res Paediatr. 2010;73:449–57.PubMed

87.

Proust-Lemoine E, Saugier-Veber P, Lefranc D, Dubucquoi S, Ryndak A, Buob D, et al. Autoimmune polyendocrine syndrome type 1 in north-western France: AIRE gene mutation specificities and severe forms needing immunosuppressive therapies. Horm Res Paediatr. 2010;74:275–84.PubMed

88.

Gylling M, Kaariainen E, Vaisanen R, Kerosuo L, Solin ML, Halme L, et al. The hypoparathyroidism of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protective effect of male sex. J Clin Endocrinol Metab. 2003;88:4602–8.PubMed

89.

Dawoodji A, Chen JL, Shepherd D, Dalin F, Tarlton A, Alimohammadi M, et al. High frequency of cytolytic 21-hydroxylase-specific CD8+ T cells in autoimmune Addison’s disease patients. J Immunol. 2014;193:2118–26.PubMed

90.

Bratland E, Skinningsrud B, Undlien DE, Mozes E, Husebye ES. T cell responses to steroid cytochrome P450 21-hydroxylase in patients with autoimmune primary adrenal insufficiency. J Clin Endocrinol Metab. 2009;94:5117–24.PubMed

91.

Rottembourg D, Deal C, Lambert M, Mallone R, Carel JC, Lacroix A, et al. 21-Hydroxylase epitopes are targeted by CD8 T cells in autoimmune Addison’s disease. J Autoimmun. 2010;35:309–15.PubMed

92.

Rosenthal FD, Davies MK, Burden AC. Malignant disease presenting as Addison’s disease. Br Med J. 1978;1:1591–2.PubMedCentralPubMed

93.

Bratland E, Husebye ES. Cellular immunity and immunopathology in autoimmune Addison’s disease. Mol Cell Endocrinol. 2011;336:180–90.PubMed

94.

Soderbergh A, Myhre AG, Ekwall O, Gebre-Medhin G, Hedstrand H, Landgren E, et al. Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab. 2004;89:557–62.PubMed

95.

Uibo R, Aavik E, Peterson P, Perheentupa J, Aranko S, Pelkonen R, et al. 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;78:323–8.PubMed

96.

Furmaniak J, Kominami S, Asawa T, Wedlock N, Colls J, Smith BR. Autoimmune Addison’s disease--evidence for a role of steroid 21-hydroxylase autoantibodies in adrenal insufficiency. J Clin Endocrinol Metab. 1994;79:1517–21.PubMed

97.

Krohn K, Uibo R, Aavik E, Peterson P, Savilahti K. Identification by molecular cloning of an autoantigen associated with Addison’s disease as steroid 17 alpha-hydroxylase. Lancet. 1992;339:770–3.PubMed

98.

Winqvist O, Karlsson FA, Kampe O. 21-Hydroxylase, a major autoantigen in idiopathic Addison’s disease. Lancet. 1992;339:1559–62.PubMed

99.

Winqvist O, Gustafsson J, Rorsman F, Karlsson FA, Kampe O. Two different cytochrome P450 enzymes are the adrenal antigens in autoimmune polyendocrine syndrome type I and Addison’s disease. J Clin Invest. 1993;92:2377–85.PubMedCentralPubMed

100.

Smith D, Stringer MD, Wyatt J, O’Meara M, Davison S, Cheetham TD, et al. Orthotopic liver transplantation for acute liver failure secondary to autoimmune hepatitis in a child with autoimmune polyglandular syndrome type 1. Pediatr Transplant. 2002;6:166–70.PubMed

101.

Abinun M, Hodges S, Cheetham T, Ognjanovic M, Hopper N, Burt A, et al. Immunomodulatory therapy for severe autoimmune polyendocrinopathy type-1 (APS-1). J Clin Immunol. 2014;34 Suppl 2:S202.

102.

Michele TM, Fleckenstein J, Sgrignoli AR, Thuluvath PJ. Chronic active hepatitis in the type I polyglandular autoimmune syndrome. Postgrad Med J. 1994;70:128–31.PubMedCentralPubMed

103.

Goldstein NS, Rosenthal P, Sinatra F, Dehner LP. Liver disease in polyglandular autoimmune disease type one: clinicopathologic study of three patients and review of the literature. Pediatr Pathol Lab Med. 1996;16:625–36.PubMed

104.

Obermayer-Straub P, Perheentupa J, Braun S, Kayser A, Barut A, Loges S, et al. Hepatic autoantigens in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. Gastroenterology. 2001;121:668–77.PubMed

105.

Kluger N, Krohn K, Ranki A. Absence of some common organ-specific and non-organ-specific autoimmunity in autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. Endocr Connect. 2013;2:61–8.PubMedCentralPubMed

106.

Gebre-Medhin G, Husebye ES, Gustafsson J, Winqvist O, Goksoyr A, Rorsman F, et al. Cytochrome P450IA2 and aromatic L-amino acid decarboxylase are hepatic autoantigens in autoimmune polyendocrine syndrome type I. FEBS Lett. 1997;412:439–45.PubMed

107.

Clemente MG, Obermayer-Straub P, Meloni A, Strassburg CP, Arangino V, Tukey RH, et al. Cytochrome P450 1A2 is a hepatic autoantigen in autoimmune polyglandular syndrome type 1. J Clin Endocrinol Metab. 1997;82:1353–61.PubMed

108.

Clemente MG, Meloni A, Obermayer-Straub P, Frau F, Manns MP, De Virgiliis S. Two cytochromes P450 are major hepatocellular autoantigens in autoimmune polyglandular syndrome type 1. Gastroenterology. 1998;114:324–8.PubMed

109.

Kluger N, Jokinen M, Krohn K, Ranki A. Gastrointestinal manifestations in APECED syndrome. J Clin Gastroenterol. 2013;47:112–20.PubMed

110.

Ward L, Paquette J, Seidman E, Huot C, Alvarez F, Crock P, 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;84:844–52.PubMed

111.

Posovszky C, Lahr G, von Schnurbein J, Buderus S, Findeisen A, Schroder C, et al. Loss of enteroendocrine cells in autoimmune-polyendocrine-candidiasis-ectodermal-dystrophy (APECED) syndrome with gastrointestinal dysfunction. J Clin Endocrinol Metab. 2012;97:E292–300.PubMed

112.

Scarpa R, Alaggio R, Norberto L, Furmaniak J, Chen S, Smith BR, et al. Tryptophan hydroxylase autoantibodies as markers of a distinct autoimmune gastrointestinal component of autoimmune polyendocrine syndrome type 1. J Clin Endocrinol Metab. 2013;98:704–12.PubMed

113.

Gianani R, Eisenbarth GS. Autoimmunity to gastrointestinal endocrine cells in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab. 2003;88:1442–4.PubMed

114.

Gunawardene AR, Corfe BM, Staton CA. Classification and functions of enteroendocrine cells of the lower gastrointestinal tract. Int J Exp Pathol. 2011;92:219–31.PubMedCentralPubMed

115.

Skoldberg F, Portela-Gomes GM, Grimelius L, Nilsson G, Perheentupa J, Betterle C, et al. Histidine decarboxylase, a pyridoxal phosphate-dependent enzyme, is an autoantigen of gastric enterochromaffin-like cells. J Clin Endocrinol Metab. 2003;88:1445–52.PubMed

116.

Ekwall O, Hedstrand H, Grimelius L, Haavik J, Perheentupa J, Gustafsson J, et al. Identification of tryptophan hydroxylase as an intestinal autoantigen. Lancet. 1998;352:279–83.PubMed

117.

Hogenauer C, Meyer RL, Netto GJ, Bell D, Little KH, Ferries L, et al. Malabsorption due to cholecystokinin deficiency in a patient with autoimmune polyglandular syndrome type I. N Engl J Med. 2001;344:270–4.PubMed

118.

Dobes J, Neuwirth A, Dobesova M, Voboril M, Balounova J, Ballek O, et al. Gastrointestinal autoimmunity associated with loss of central tolerance to enteric alpha-defensins. Gastroenterology. 2015;149:139–50.

119.

Hedstrand H, Ekwall O, Haavik J, Landgren E, Betterle C, Perheentupa J, et al. Identification of tyrosine hydroxylase as an autoantigen in autoimmune polyendocrine syndrome type I. Biochem Biophys Res Commun. 2000;267:456–61.PubMed

120.

Hedstrand H, Ekwall O, Olsson MJ, Landgren E, Kemp EH, Weetman AP, et al. The transcription factors SOX9 and SOX10 are vitiligo autoantigens in autoimmune polyendocrine syndrome type I. J Biol Chem. 2001;276:35390–5.PubMed

121.

Al-Owain M, Kaya N, Al-Zaidan H, Bin Hussain I, Al-Manea H, Al-Hindi H, et al. Renal failure associated with APECED and terminal 4q deletion: evidence of autoimmune nephropathy. Clin Dev Immunol. 2010;2010:586342.PubMedCentralPubMed

122.

Ulinski T, Perrin L, Morris M, Houang M, Cabrol S, Grapin C, et al. Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome with renal failure: impact of posttransplant immunosuppression on disease activity. J Clin Endocrinol Metab. 2006;91:192–5.PubMed

123.

Alimohammadi M, Dubois N, Skoldberg F, Hallgren A, Tardivel I, Hedstrand H, et al. Pulmonary autoimmunity as a feature of autoimmune polyendocrine syndrome type 1 and identification of KCNRG as a bronchial autoantigen. Proc Natl Acad Sci U S A. 2009;106:4396–401.PubMedCentralPubMed

124.

Popler J, Alimohammadi M, Kampe O, Dalin F, Dishop MK, Barker JM, et al. Autoimmune polyendocrine syndrome type 1: Utility of KCNRG autoantibodies as a marker of active pulmonary disease and successful treatment with rituximab. Pediatr Pulmonol. 2012;47:84–7.PubMed

125.

Shum AK, Alimohammadi M, Tan CL, Cheng MH, Metzger TC, Law CS, et al. BPIFB1 is a lung-specific autoantigen associated with interstitial lung disease. Sci Transl Med. 2014;5:206ra139.

126.

Su MA, Davini D, Cheng P, Giang K, Fan U, DeVoss JJ, et al. Defective autoimmune regulator-dependent central tolerance to myelin protein zero is linked to autoimmune peripheral neuropathy. J Immunol. 2012;188:4906–12.PubMedCentralPubMed

127.

Di Sabatino A, Carsetti R, Corazza GR. Post-splenectomy and hyposplenic states. Lancet. 2011;378:86–97.PubMed

128.

Husebye ES. Functional autoantibodies cause hypoparathyroidism. J Clin Endocrinol Metab. 2009;94:4655–7.PubMed

129.

Improda N, Capalbo D, Cirillo E, Cerbone M, Esposito A, Pignata C, et al. Cutaneous vasculitis in patients with autoimmune polyendocrine syndrome type 1: report of a case and brief review of the literature. BMC Pediatr. 2014;14:272.PubMedCentralPubMed

130.

Zhang SY, Boisson-Dupuis S, Chapgier A, Yang K, Bustamante J, Puel A, et al. Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the respective roles of IFN-alpha/beta, IFN-gamma, and IFN-lambda in host defense. Immunol Rev. 2008;226:29–40.PubMed

131.

Oftedal BE, Kampe O, Meager A, Ahlgren KM, Lobell A, Husebye ES, et al. Measuring autoantibodies against IL-17F and IL-22 in autoimmune polyendocrine syndrome type I by radioligand binding assay using fusion proteins. Scand J Immunol. 2011;74:327–33.PubMed

132.

Alimohammadi M, Bjorklund P, Hallgren A, Pontynen N, Szinnai G, Shikama N, et al. Autoimmune polyendocrine syndrome type 1 and NALP5, a parathyroid autoantigen. N Engl J Med. 2008;358:1018–28.PubMed

133.

Gavalas NG, Kemp EH, Krohn KJ, Brown EM, Watson PF, Weetman AP. The calcium-sensing receptor is a target of autoantibodies in patients with autoimmune polyendocrine syndrome type 1. J Clin Endocrinol Metab. 2007;92:2107–14.PubMed

134.

Kemp EH, Habibullah M, Kluger N, Ranki A, Sandhu HK, Krohn KJ, et al. Prevalence and clinical associations of calcium-sensing receptor and NALP5 autoantibodies in Finnish APECED patients. J Clin Endocrinol Metab. 2014;99:1064–71.PubMed

135.

Eisenbarth GS. Do NALP5 antibodies correlate with hypoparathyroidism in patients with APS-1? Nat Clin Pract Endocrinol Metab. 2008;4:544–5.PubMed

136.

Gylling M, Tuomi T, Bjorses P, Kontiainen S, Partanen J, Christie MR, et al. ss-cell autoantibodies, human leukocyte antigen II alleles, and type 1 diabetes in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Clin Endocrinol Metab. 2000;85:4434–40.PubMed

137.

Bratland E, Magitta NF, Boe Wolff AS, Ekern T, Knappskog PM, Kampe O, et al. Autoantibodies against aromatic amino acid hydroxylases in patients with autoimmune polyendocrine syndrome type 1 target multiple antigenic determinants and reveal regulatory regions crucial for enzymatic activity. Immunobiology. 2013;218:899–909.PubMed

138.

Husebye ES, Gebre-Medhin G, Tuomi T, Perheentupa J, Landin-Olsson M, Gustafsson J, et al. Autoantibodies against aromatic L-amino acid decarboxylase in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab. 1997;82:147–50.PubMed

139.

Bensing S, Fetissov SO, Mulder J, Perheentupa J, Gustafsson J, Husebye ES, et al. Pituitary autoantibodies in autoimmune polyendocrine syndrome type 1. Proc Natl Acad Sci U S A. 2007;104:949–54.PubMedCentralPubMed

140.

Reimand K, Perheentupa J, Link M, Krohn K, Peterson P, Uibo R. Testis-expressed protein TSGA10 an auto-antigen in autoimmune polyendocrine syndrome type I. Int Immunol. 2008;20:39–44.PubMed

141.

Anderson MS, Su MA. Aire and T cell development. Curr Opin Immunol. 2010;23:198–206.PubMedCentralPubMed

142.

Teh CE, Daley SR, Enders A, Goodnow CC. T-cell regulation by casitas B-lineage lymphoma (Cblb) is a critical failsafe against autoimmune disease due to autoimmune regulator (Aire) deficiency. Proc Natl Acad Sci U S A. 2010;107:14709–14.PubMedCentralPubMed

143.

Meager A, Peterson P, Willcox N. Hypothetical review: thymic aberrations and type-I interferons; attempts to deduce autoimmunizing mechanisms from unexpected clues in monogenic and paraneoplastic syndromes. Clin Exp Immunol. 2008;154:141–51.PubMedCentralPubMed

144.

Kisand K, Peterson P. Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy: known and novel aspects of the syndrome. Ann N Y Acad Sci. 2012;1246:77–91.

145.

Wolff AS, Karner J, Owe JF, Oftedal BE, Gilhus NE, Erichsen MM, et al. Clinical and serologic parallels to APS-I in patients with thymomas and autoantigen transcripts in their tumors. J Immunol. 2014;193:3880–90.PubMedCentralPubMed

146.

Strobel P, Murumagi A, Klein R, Luster M, Lahti M, Krohn K, et al. Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS-1). J Pathol. 2007;211:563–71.PubMed

147.

Laakso SM, Kekalainen E, Rossi LH, Laurinolli TT, Mannerstrom H, Heikkila N, et al. IL-7 Dysregulation and Loss of CD8+ T Cell Homeostasis in the Monogenic Human Disease Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy. J Immunol. 2011;187:2023–30.PubMed

148.

Wolff AS, Oftedal BE, Kisand K, Ersvaer E, Lima K, Husebye ES. Flow cytometry study of blood cell subtypes reflects autoimmune and inflammatory processes in autoimmune polyendocrine syndrome type I. Scand J Immunol. 2010;71:459–67.PubMed

149.

Kekalainen E, Tuovinen H, Joensuu J, Gylling M, Franssila R, Pontynen N, et al. A defect of regulatory T cells in patients with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy. J Immunol. 2007;178:1208–15.PubMed

150.

Laakso SM, Laurinolli TT, Rossi LH, Lehtoviita A, Sairanen H, Perheentupa J, et al. Regulatory T cell defect in APECED patients is associated with loss of naive FOXP3(+) precursors and impaired activated population. J Autoimmun. 2010;35:351–7.PubMed

151.

Ryan KR, Lawson CA, Lorenzi AR, Arkwright PD, Isaacs JD, Lilic D. CD4+CD25+ T-regulatory cells are decreased in patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy. J Allergy Clin Immunol. 2005;116:1158–9.PubMed

152.

Mathis D, Benoist C. Aire. Annu Rev Immunol. 2009;27:287–312.PubMed

153.

Padeh S, Theodor R, Jonas A, Passwell JH. Severe malabsorption in autoimmune polyendocrinopathy-candidosis-ectodermal dystrophy syndrome successfully treated with immunosuppression. Arch Dis Child. 1997;76:532–4.PubMedCentralPubMed

154.

O’Gorman CS, Shulman R, Lara-Corrales I, Pope E, Marcon M, Grasemann H, et al. A child with autoimmune polyendocrinopathy candidiasis and ectodermal dysplasia treated with immunosuppression: a case report. J Med Case Rep. 2013;7:44.PubMedCentralPubMed

155.

York M, Sargur R, Shrimpton W, Egner W. Successful managment of APECED with Rituximab. J Clin Immunol. 2014;34 Suppl 2:S233.

156.

Bakrac M, Jurisic V, Kostic T, Popovic V, Pekic S, Kraguljac N, et al. Pure red cell aplasia associated with type I autoimmune polyglandular syndrome-successful response to treatment with mycophenolate mofetil: case report and review of literature. J Clin Pathol. 2007;60:717–20.PubMedCentralPubMed

157.

Perniola R, Falorni A, Clemente MG, Forini F, Accogli E, Lobreglio G. Organ-specific and non-organ-specific autoantibodies in children and young adults with autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED). Eur J Endocrinol. 2000;143(4):497–503.PubMed

158.

Dal Pra C, Chen S, Betterle C, Zanchetta R, McGrath V, Furmaniak J, et al. Autoantibodies to human tryptophan hydroxylase and aromatic L-amino acid decarboxylase. Eur J Endocrinol. 2004;150(3):313–21.PubMed

159.

Candeloro P, Voltattorni CB, Perniola R, Bertoldi M, Betterle C, Mannelli M, et al. Mapping of human autoantibody epitopes on aromatic L-amino acid decarboxylase. J Clin Endocrinol Metab. 2007;92(3):1096–105.PubMed

Titel: Autoimmune Polyendocrinopathy Candidiasis Ectodermal Dystrophy
verfasst von: Kai Kisand
Pärt Peterson
Publikationsdatum: 01.07.2015
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 5/2015
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-015-0176-y

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2015

IL2RG Reversion Event in a Common Lymphoid Progenitor Leads to Delayed Diagnosis and Milder Phenotype

A Homozygous CARD9 Mutation in a Brazilian Patient with Deep Dermatophytosis

Somatic Mosaicism for a NRAS Mutation Associates with Disparate Clinical Features in RAS-associated Leukoproliferative Disease: a Report of Two Cases

Late-Onset Severe Chronic Active EBV in a Patient for Five Years with Mutations in STXBP2 (MUNC18-2) and PRF1 (Perforin 1)

Lung Magnetic Resonance Imaging with Diffusion Weighted Imaging Provides Regional Structural as well as Functional Information Without Radiation Exposure in Primary Antibody Deficiencies