학술논문
Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients
Document Type
Original Paper
Author
Garelli, S.; Dalla Costa, M.; Sabbadin, C.; Barollo, S.; Rubin, B.; Scarpa, R.; Masiero, S.; Fierabracci, A.; Bizzarri, C.; Crinò, A.; Cappa, M.; Valenzise, M.; Meloni, A.; De Bellis, A. M.; Giordano, C.; Presotto, F.; Perniola, R.; Capalbo, D.; Salerno, M. C.; Stigliano, A.; Radetti, G.; Camozzi, V.; Greggio, N. A.; Bogazzi, F.; Chiodini, I.; Pagotto, U.; Black, S. K.; Chen, S.; Rees Smith, B.; Furmaniak, J.; Weber, G.; Pigliaru, F.; De Sanctis, L.; Scaroni, C.; Betterle, C.
Source
Journal of Endocrinological Investigation: Official Journal of Italian Society of Endocrinology (SIE). 44(11):2493-2510
Subject
Language
English
ISSN
1720-8386
Abstract
Background: Autoimmune Polyglandular Syndrome type 1 (APS-1) is a rare recessive inherited disease, caused by AutoImmune Regulator (AIRE) gene mutations and characterized by three major manifestations: chronic mucocutaneous candidiasis (CMC), chronic hypoparathyroidism (CH) and Addison’s disease (AD).Methods: Autoimmune conditions and associated autoantibodies (Abs) were analyzed in 158 Italian patients (103 females and 55 males; F/M 1.9/1) at the onset and during a follow-up of 23.7 ± 15.1 years. AIRE mutations were determined.Results: The prevalence of APS-1 was 2.6 cases/million (range 0.5–17 in different regions). At the onset 93% of patients presented with one or more components of the classical triad and 7% with other components. At the end of follow-up, 86.1% had CH, 77.2% AD, 74.7% CMC, 49.5% premature menopause, 29.7% autoimmune intestinal dysfunction, 27.8% autoimmune thyroid diseases, 25.9% autoimmune gastritis/pernicious anemia, 25.3% ectodermal dystrophy, 24% alopecia, 21.5% autoimmune hepatitis, 17% vitiligo, 13.3% cholelithiasis, 5.7% connective diseases, 4.4% asplenia, 2.5% celiac disease and 13.9% cancer. Overall, 991 diseases (6.3 diseases/patient) were found. Interferon-ω Abs (IFNωAbs) were positive in 91.1% of patients. Overall mortality was 14.6%. The AIRE mutation R139X was found in 21.3% of tested alleles, R257X in 11.8%, W78R in 11.4%, C322fsX372 in 8.8%, T16M in 6.2%, R203X in 4%, and A21V in 2.9%. Less frequent mutations were present in 12.9%, very rare in 9.6% while no mutations in 11% of the cases.Conclusions: In Italy, APS-1 is a rare disorder presenting with the three major manifestations and associated with different AIRE gene mutations. IFNωAbs are markers of APS-1 and other organ-specific autoantibodies are markers of clinical, subclinical or potential autoimmune conditions.