AUTOIMMUNE POLYENDOCRINOPATHY-CANDIDIASIS-ECTODERMAL DYSTROPHY (APECED)

SCIENTIFIC BACKGROUND

APECED syndrome, or autoimmune polyendocrinopathy type 1, is an autosomal recessive inherited autoimmune disease caused by pathogenic variants in the AIRE gene, which is an autoimmune regulatory gene. The disease begins in childhood and is characterized by at least two of the following leading symptoms:

• Addison's disease
• Hypoparathyroidism
• chronic candidiasis of the skin and mucous membranes without a generalized infestation

Additionally, other endocrine diseases caused by autoimmune processes may develop, such as diabetes mellitus type 1, thyroiditis, and hypergonadotropic hypogonadism. The autoimmunological changes may also affect other organs, resulting, for example, in dystrophy of ectodermal structures (enamel and nail dystrophy, alopecia, vitiligo, keratitis), pernicious anemia in chronic atrophic gastritis, or chronic active hepatitis. However, candidiasis is usually the first symptom. Pathogenic variants in the AIRE gene are detectable in almost all patients with two of the three leading symptoms. APECED is more common in certain populations, such as Finns (1:25,000), Sardinians (1:14,000), and Iraqi Jews (1:9,000). Certain pathogenic variants occur clustered in individual populations. For example, nearly 90% of Finnish affected individuals are carriers of the pathogenic variant Arg257Ter. The AIRE gene comprises 14 exons and is primarily expressed in tissues crucial for the maturation of the immune system, such as the thymus, lymph nodes, and fetal liver.

References
Weiler et al. 2018, Clin Immunol 197:231 / Orlova et al. 2017, J Clin Endocrinol Metab 102:3546 / Oftedal et al. 2015, Immunity 42:1185 / Eisenbarth et al. 2004, N Eng J Med 350:2068 / Cihakova et al. 2001, Hum Mutat 18:225 / Ahonen et al. 1990, N Eng J Med 322:1829