Autoimmune polyendocrine syndrome type 1
Autoimmune condition causing dysfunction of endocrine glands
Medical condition
Autoimmune polyendocrine syndrome type 1 (APS-1 ), is a subtype of autoimmune polyendocrine syndrome (autoimmune polyglandular syndrome). It causes the dysfunction of multiple endocrine glands due to autoimmunity . It is a genetic disorder , inherited in autosomal recessive fashion due to a defect in the AIRE gene (autoimmune regulator) , which is located on chromosome 21 and normally confers immune tolerance .[ 1] [ 2] [ 3]
Signs and symptoms
APS-1 tends to cause severe symptoms.[ 4] These are present from early in life, usually around 3.5 years of age.[ 4] Common symptoms of APS-1 include:
APS-1 may also cause:
Cause
Chromosome 21
APS-1 is caused by a mutation in the AIRE gene , encoding a protein called autoimmune regulator. This is found on the 21q22.3 chromosome location, hence chromosome 21 .[ 1] [ 2] [ 6] The AIRE gene may be affected by any of at least 186 mutations .[ 7] APS-1 may be inherited in an autosomal recessive manner.[ 8]
Different mutations are more common in different geographic regions. R139X is a common mutation in Sardinia .[ 4] R257* is a common mutation in Finland .[ 5] Both of these mutations are nonsense mutations : the asterisk and the "X" both indicate a stop codon .[ 7] A 13-base-pair deletion in the AIRE gene, c.967-979del13bp, has been identified in APS-1 patients in Norway , Britain [ 8] and North America .[ 9] [ 10]
Pathophysiology
APS-1 is due to problems with immune tolerance .[ 11] APS-1 causes considerable reactions with both interferon omega and interferon alpha .[ 4] [ 12] There may also be a reaction against interleukin 22 .[ 4] This leads to damage to endocrine organs.[ 4] Common problems include hypercalcaemia and nephrocalcinosis (due to a lack of calcitonin from the thyroid ), and pituitary problems (such as growth hormone deficiency ).[ 4] Antibodies against NLRP5 may lead to hypoparathyroidism .[citation needed ]
Diagnosis
Endoscope
Diagnosis of APS-1 is based on a number of tests, including endoscopy , a CT scan ,[ 12] a biopsy (with histological testing),[ 12] and serum endocrine autoantibody screening.
Treatment
Autoimmune polyendocrine syndrome type 1 treatment is based on the symptoms that are presented by the affected individual. Treatments may involve hormone therapy ,[ 13] systemic antifungal treatments,[ 4] [ 13] and immunosuppression .[ 13] The JAK-STAT inhibitor ruxolitinib is being investigated as a treatment specifically for its normalizing effect on interferon-gamma .[ 14]
History
APS-1 may also be known as autoimmunity endocrinopathy candidiasis ectodermal dystrophy / dysplasia (APECED),[citation needed ] autoimmune polyglandular syndrome type 1,[citation needed ] Whitaker syndrome,[ 12] or candidiasis-hypoparathyroidism-Addison's disease syndrome.[ 15]
See also
References
^ a b "AIRE gene" . Genetics Home Reference . Archived from the original on 2017-04-05. Retrieved 2017-04-04 .
^ a b "APECED" . Archived from the original on 2017-04-06. Retrieved 2017-04-04 .
^ Shoenfeld Y, Cervera R, Gershwin ME (2010-06-08). Diagnostic Criteria in Autoimmune Diseases . Springer Science & Business Media. p. 265. ISBN 9781603272858 . Archived from the original on 2023-01-14. Retrieved 2020-11-05 .
^ a b c d e f g h i j k l m n o Meloni, Antonella; Willcox, Nick; Meager, Anthony; Atzeni, Michela; Wolff, Anette S. B.; Husebye, Eystein S.; Furcas, Maria; Rosatelli, Maria Cristina; Cao, Antonio; Congia, Mauro (April 2012). "Autoimmune Polyendocrine Syndrome Type 1: An Extensive Longitudinal Study in Sardinian Patients" . The Journal of Clinical Endocrinology & Metabolism . 97 (4): 1114–1124. doi :10.1210/jc.2011-2461 . ISSN 0021-972X . PMID 22344197 .
^ a b Orlova, Elizaveta M; Sozaeva, Leila S; Kareva, Maria A; Oftedal, Bergithe E; Wolff, Anette S B; Breivik, Lars; Zakharova, Ekaterina Y; Ivanova, Olga N; Kämpe, Olle; Dedov, Ivan I; Knappskog, Per M (2017-07-20). "Expanding the Phenotypic and Genotypic Landscape of Autoimmune Polyendocrine Syndrome Type 1" . The Journal of Clinical Endocrinology & Metabolism . 102 (9): 3546–3556. doi :10.1210/jc.2017-00139 . ISSN 0021-972X . PMID 28911151 . S2CID 3822560 .
^ "Autoimmune Polyglandular Syndrome Type 1 (APS-1)" . NIH: National Institute of Allergy and Infectious Diseases . Archived from the original on 2017-04-17. Retrieved 2017-04-16 .
^ a b D.N. Cooper; E.V. Ball; P.D. Stenson; A.D. Phillips; K. Evans; S. Heywood; M.J. Hayden; M.M. Chapman; M.E Mort; L. Azevedo; D.S. Millar (eds.). "AIRE" . The Human Gene Mutation Database . Institute of Medical Genetics in Cardiff. Archived from the original on 22 August 2023. Retrieved 22 August 2023 .
^ a b 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" . American Journal of Human Genetics . 63 (6): 1675–1684. doi :10.1086/302145 . PMC 1377639 . PMID 9837820 .
^ Bruserud Ø, Oftedal BE, Wolff AB, Husebye ES (2016). "AIRE -mutations and autoimmune disease". Current Opinion in Immunology . 43 : 8–15. doi :10.1016/j.coi.2016.07.003 . PMID 27504588 .
^ Qian G, Yan X, Xuan J, Zheng D, He Z, Shen J (2022). "A novel AIRE mutation leads to autoimmune polyendocrine syndrome type-1" . Frontiers in Cell and Developmental Biology . 10 . doi :10.3389/fcell.2022.948350 . PMC 9441485 . PMID 36072346 . 948350.
^ De Martino L, Capalbo D, Improda N, D'Elia F, Di Mase R, D'Assante R, et al. (October 2013). "APECED: A Paradigm of Complex Interactions between Genetic Background and Susceptibility Factors" . Frontiers in Immunology . 4 : 331. doi :10.3389/fimmu.2013.00331 . PMC 3805967 . PMID 24167503 .
^ a b c d Aldasouqi, Saleh A. (15 November 2016). "Type I Polyglandular Autoimmune Syndrome" . emedicine.medscape.com . Medscape. Archived from the original on 2008-12-09. Retrieved 20 November 2020 .
^ a b c INSERM RESERVED. "Orphanet: Autoimmune polyendocrinopathy type 1" . www.orpha.net . Archived from the original on 2017-04-23. Retrieved 2017-04-22 .
^ Oikonomou, Vasileios; Smith, Grace; Constantine, Gregory M.; Schmitt, Monica M.; Ferré, Elise M.N.; Alejo, Julie C.; Riley, Deanna; Kumar, Dhaneshwar; Dos Santos Dias, Lucas; Pechacek, Joseph; Hadjiyannis, Yannis; Webb, Taura; Seifert, Bryce A.; Ghosh, Rajarshi; Walkiewicz, Magdalena (2024-05-30). "The Role of Interferon-γ in Autoimmune Polyendocrine Syndrome Type 1" . New England Journal of Medicine . 390 (20): 1873–1884. doi :10.1056/NEJMoa2312665 . ISSN 0028-4793 .
^ Greenspan, F. S.; Gardner, D. C. (2004). Basic clinical endocrinology . New York : McGraw-Hill . pp. 103 . ISBN 978-0-07-140297-2 .
Further reading
De Martino L, Capalbo D, Improda N, Lorello P, Ungaro C, Di Mase R, et al. (1 January 2016). "Novel Findings into AIRE Genetics and Functioning: Clinical Implications" . Frontiers in Pediatrics . 4 : 86. doi :10.3389/fped.2016.00086 . PMC 4992815 . PMID 27597936 .
Peterson P, Pitkänen J, Sillanpää N, Krohn K (March 2004). "Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED): a model disease to study molecular aspects of endocrine autoimmunity" . Clinical and Experimental Immunology . 135 (3): 348–57. doi :10.1111/j.1365-2249.2004.02384.x . PMC 1808970 . PMID 15008965 .
Capalbo D, De Martino L, Giardino G, Di Mase R, Di Donato I, Parenti G, et al. (2012). "Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy: insights into genotype-phenotype correlation" . International Journal of Endocrinology . 2012 : 353250. doi :10.1155/2012/353250 . PMC 3485503 . PMID 23133448 .
External links
Classification External resources
(1) Basic domains
(2) Zinc finger DNA-binding domains
(3) Helix-turn-helix domains
(4) β-Scaffold factors with minor groove contacts
(0) Other transcription factors
Ungrouped Transcription coregulators