1. Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients
- Author
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F. Bogazzi, Giorgio Radetti, Mariacarolina Salerno, B. Rees Smith, Stefano Masiero, L. de Sanctis, F. Presotto, Carla Giordano, Roberto Perniola, Valentina Camozzi, C. Betterle, Carla Scaroni, Antonella Meloni, Sarah Black, Francesca Pigliaru, Chiara Sabbadin, Alessandra Fierabracci, Carla Bizzarri, Marco Cappa, Garvin Weber, Donatella Capalbo, Susi Barollo, Jadwiga Furmaniak, Mariella Valenzise, Antonio Stigliano, A. Crinò, N. A. Greggio, Riccardo Scarpa, Silvia Garelli, Uberto Pagotto, M. Dalla Costa, A. De Bellis, Iacopo Chiodini, Shu Chen, Beatrice Rubin, Garelli, S., Dalla Costa, M., Sabbadin, C., Barollo, S., Rubin, B., Scarpa, R., Masiero, S., Fierabracci, A., Bizzarri, C., Crino, A., Cappa, M., Valenzise, M., Meloni, A., De Bellis, A. M., Giordano, C., Presotto, F., Perniola, R., Capalbo, D., Salerno, M., 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., Garelli S., Dalla Costa M., Sabbadin C., Barollo S., Rubin B., Scarpa R., Masiero S., Fierabracci A., Bizzarri C., Crino 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., 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, and Betterle, C
- Subjects
Male ,Transcription Factor ,Endocrinology, Diabetes and Metabolism ,Autoimmune hepatitis ,Gene mutation ,Gastroenterology ,Chronic mucocutaneous candidiasis ,Endocrinology ,Addison Disease ,Autoimmune Polyglandular Syndrome type 1 (APS-1) ,Prevalence ,Medicine ,Polyendocrinopathies, Autoimmune ,Candidiasis, Chronic Mucocutaneou ,Addison’s disease, AIRE gene mutations, Autoimmune Polyglandular Syndrome type 1 (APS-1), Autoimmune-poly-endocrine-candidiasis-ectodermal-dystrophy (APECED), Chronic hypoparathyroidism, Chronic mucocutaneous candidiasis, Interferon autoantibodies ,Candidiasis, Chronic Mucocutaneous ,AIRE gene mutations ,Addison’s disease ,autoimmune polyglandular syndrome type 1 (APS-1) ,autoimmune-poly-endocrine-candidiasis-ectodermal-dystrophy (APECED) ,chronic hypoparathyroidism ,chronic mucocutaneous candidiasis ,interferon autoantibodies ,Autoimmune regulator ,Autoantibodie ,Italy ,Interferon autoantibodie ,Addison's disease ,Interferon Type I ,Original Article ,Female ,Chronic hypoparathyroidism ,Human ,Adult ,medicine.medical_specialty ,Autoimmune Gastritis ,Hypoparathyroidism ,Internal medicine ,Interferon autoantibodies ,Humans ,Mortality ,Autoantibodies ,Autoimmune-poly-endocrine-candidiasis-ectodermal-dystrophy (APECED) ,business.industry ,Chronic mucocutaneous candidiasi ,AIRE gene mutation ,Autoantibody ,medicine.disease ,Autoimmune polyendocrine syndrome type 1 ,Mutation ,business ,Transcription Factors - 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.
- Published
- 2021