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.

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients / 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.. - In: JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION. - ISSN 0391-4097. - ELETTRONICO. - 44:11(2021), pp. 2493-2510. [10.1007/s40618-021-01585-6]

Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients

Garelli S.;Pagotto U.;
2021

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.
2021
Autoimmune polyendocrine syndrome type 1: an Italian survey on 158 patients / 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.. - In: JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION. - ISSN 0391-4097. - ELETTRONICO. - 44:11(2021), pp. 2493-2510. [10.1007/s40618-021-01585-6]
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.
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