Endocrinology Research Centre, Institute of Paediatric Endocrinology, Moscow 117036, Russia.
I. M. Sechenov First Moscow State Medical University, Moscow 117036, Russia.
J Clin Endocrinol Metab. 2017 Sep 1;102(9):3546-3556. doi: 10.1210/jc.2017-00139.
Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare monogenic autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene and characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. Comprehensive characterizations of large patient cohorts are rare.
To perform an extensive clinical, immunological, and genetic characterization of a large nationwide Russian APS-1 cohort.
Clinical components were mapped by systematic investigations, sera were screened for autoantibodies associated with APS-1, and AIRE mutations were characterized by Sanger sequencing.
We identified 112 patients with APS-1, which is, to the best of our knowledge, the largest cohort described to date. Careful phenotyping revealed several additional and uncommon phenotypes such as cerebellar ataxia with pseudotumor, ptosis, and retinitis pigmentosa. Neutralizing autoantibodies to interferon-ω were found in all patients except for one. The major Finnish mutation c.769C>T (p.R257*) was the most frequent and was present in 72% of the alleles. Altogether, 19 different mutations were found, of which 9 were unknown: c.38T>C (p.L13P), c.173C>T (p.A58V), c.280C>T (p.Q94*), c.554C>G (p.S185*), c.661A>T (p.K221*), c.821del (p.Gly274Afs104), c.1195G>C (p.A399P), c.1302C>A (p.C434), and c.1497del (p.A500Pfs*21).
The spectrum of phenotypes and AIRE mutation in APS-1 has been expanded. The Finnish major mutation is the most common mutation in Russia and is almost as common as in Finland. Assay of interferon antibodies is a robust screening tool for APS-1.
自身免疫性多内分泌腺综合征 1 型（APS-1）是一种罕见的单基因自身免疫性疾病，由自身免疫调节因子（AIRE）基因突变引起，其特征为慢性黏膜皮肤念珠菌病、甲状旁腺功能减退症和原发性肾上腺功能不全。对大型患者队列进行全面的特征描述较为罕见。
对俄罗斯 APS-1 大型全国性队列进行广泛的临床、免疫和遗传特征描述。
通过系统调查对临床特征进行了映射，对血清进行了与 APS-1 相关的自身抗体筛查，并通过 Sanger 测序对 AIRE 突变进行了特征描述。
我们共鉴定了 112 例 APS-1 患者，这是迄今为止描述的最大队列。仔细表型分析揭示了其他几种不常见的表型，如小脑共济失调伴假性肿瘤、上睑下垂和色素性视网膜炎。除了 1 例患者外，所有患者均存在中和干扰素-ω的自身抗体。主要的芬兰突变 c.769C>T（p.R257*）是最常见的突变，存在于 72%的等位基因中。共发现 19 种不同的突变，其中 9 种为未知突变：c.38T>C（p.L13P）、c.173C>T（p.A58V）、c.280C>T（p.Q94*）、c.554C>G（p.S185*）、c.661A>T（p.K221*）、c.821del（p.Gly274Afs104）、c.1195G>C（p.A399P）、c.1302C>A（p.C434）和 c.1497del（p.A500Pfs*21）。
APS-1 的表型谱和 AIRE 突变已得到扩展。芬兰的主要突变是俄罗斯最常见的突变，与芬兰一样常见。干扰素抗体检测是 APS-1 的一种可靠筛查工具。
