Abstract
Autoimmune polyglandular syndrome type 1 (APS-1), also called Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy (APECED; OMIM 240300) according to the spectrum of clinical features, is a rarebut very serious monogenic condition. Clinically,APS-1 is characterized by at least two of three major components- mucocutaneous candidiasis, hypoparathyroidism and Addison's disease.
During the lifespan, immune-mediatedfailure of additional endocrine glands and some non-endocrine organs usually develops. The defective gene inAPS-1was discovered in 1997,mapped to chromosome 21 (21q22.3) and is referred to as AIRE (Autoimmune Regulator).It encodes a transcription factor (AIRE protein) expressed mainly in the thymus and lymph nodes.
AIRE probablysubstantially contributes to the establishment of central immune tolerance. Authors analyzed the clinical courseof APS-1 in 22 children and young adults from 5 Central- and Eastern-European countries (age 4 - 22 years, median16) with previously detected AIRE gene defects.
The first sign of the disorder appeared at 0.3 - 16 years (median6). The earliest and most frequent disease components included hypoparathyroidism (91 % patients) and/ormucocutaneous candidiasis (82 %) which manifested from the first year of life.
Addison's disease developed in82%of patients not earlier than at the age of 4 years. Less frequent disease components included hypothyroidism(32%of subjects; diagnosed after the 7th year), atrophic gastritis (27 %; after the 6th year) and some others.
Thediagnosis of APS-1 makes possible a consistent follow-up, early detection and therapy of additional features. Thefuture research on AIRE gene and AIRE protein may contribute to the understanding of basic mechanisms ofimmune tolerance, and possibly to the development of new therapies of autoimmune conditions.