自身免疫性多内分泌腺综合征 1 型：意大利 158 例患者的调查。

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

机构信息

Endocrine Unit, Department of Medicine (DIMED), University of Padua, Via Ospedale Civile 105, 35128, Padua, Italy.

Unit of Internal Medicine, Ospedale dell'Angelo, Mestre-Venice, Italy.

出版信息

J Endocrinol Invest. 2021 Nov;44(11):2493-2510. doi: 10.1007/s40618-021-01585-6. Epub 2021 May 18.

DOI:10.1007/s40618-021-01585-6

PMID:34003463

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8502131/

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.

摘要

背景

自身免疫性多腺体综合征 1 型（APS-1）是一种罕见的隐性遗传性疾病，由自身免疫调节（AIRE）基因突变引起，其特征为三大表现：慢性黏膜皮肤念珠菌病（CMC）、慢性甲状旁腺功能减退症（CH）和艾迪生病（AD）。

方法

在意大利的 158 例患者（103 名女性和 55 名男性；F/M 为 1.9/1）中，在发病时和 23.7±15.1 年的随访期间，分析了自身免疫性疾病和相关自身抗体（Abs）。测定了 AIRE 突变。

结果

APS-1 的患病率为每百万 2.6 例（不同地区为 0.5-17）。发病时，93%的患者有一个或多个经典三联征的表现，7%的患者有其他表现。随访结束时，86.1%的患者有 CH，77.2%的患者有 AD，74.7%的患者有 CMC，49.5%的患者有过早绝经，29.7%的患者有自身免疫性肠功能障碍，27.8%的患者有自身免疫性甲状腺疾病，25.9%的患者有自身免疫性胃炎/恶性贫血，25.3%的患者有外胚层发育不良，24%的患者有脱发，21.5%的患者有自身免疫性肝炎，17%的患者有白癜风，13.3%的患者有胆石症，5.7%的患者有结缔组织疾病，4.4%的患者有脾切除，2.5%的患者有乳糜泻，13.9%的患者有癌症。共发现 991 种疾病（6.3 种/患者）。91.1%的患者有干扰素-ω Abs（IFNωAbs）阳性。总死亡率为 14.6%。在检测的等位基因中，R139X 突变占 21.3%，R257X 突变占 11.8%，W78R 突变占 11.4%，C322fsX372 突变占 8.8%，T16M 突变占 6.2%，R203X 突变占 4%，A21V 突变占 2.9%。12.9%的患者有较不常见的突变，9.6%的患者有罕见的突变，11%的患者没有突变。