Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1) associated with compound heterozygous novel AIRE gene mutations
Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1) associated with compound heterozygous novel AIRE gene mutations
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DOI：
10.1006/clim.2002.5208
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发表时间：
2002-06-01
影响因子：
8.6
通讯作者：
Shimizu, N
中科院分区：
文献类型：
--
作者：
Kogawa, K;Kudoh, J;Shimizu, N
我们在此报告两个患有自身免疫性多腺体综合征1型(APS-1)的日本兄弟姐妹。这个哥哥表现出APS-1的特征表型，在婴儿早期就患上了严重的粘膜皮肤念珠菌病，此后发展为甲状旁腺功能减退症和爱迪生病，同时他的免疫功能严重恶化。相比之下，44岁的姐姐表现出非特征性的APS-1表型，发展为胰岛素依赖型糖尿病，具有高抗谷氨酸脱羧酶抗体，轻度指甲念珠菌病，以及免疫反应完整的自身免疫性肝炎。她有三个易患I型自身免疫性糖尿病的人类白细胞抗原(HL A)基因。T细胞受体(TCR)Vbeta5.1的表达在两个患者中都增加了，而兄弟表现出许多TCRVβ家族的广泛抑制表达。两人均具有新型自身免疫调节因子(AIRE)杂合性基因突变(L29P和IVS9-1G>；C)。因此，相同的AIRE基因突变可能与APS-1的特征表型和非特征表型相关，而人类白细胞抗原可能影响APS-1的表型。(C)2002年埃尔塞维尔科学公司(美国)。
We herein report on two Japanese siblings with antoimmune polyglandular syndrome type 1 (APS-1). The brother, who expressed a characteristic phenotype of APS-1, had developed severe mucocutaneous candidiasis in early infancy and thereafter developed hypoparathyroidism and Addison's disease, along with a severe deterioration of his immunologic function. In contrast, the 44-year-old sister, who showed a noncharacteristic phenotype of APS-1, developed insulin-dependent diabetes with high anti-glutamic acid decarboxylase antibody, mild nail candidiasis, and autoimmune hepatitis with intact immunoreactivity. She had three susceptible human leukocyte antigen (HLA) loci for type I autoimmune diabetes. The expression of T cell receptor (TCR)Vbeta5.1 increased in both patients, while the brother showed a widely suppressed expression of many TCRVbeta families. Both individuals possessed compound heterozygous novel autoimmune regulator (AIRE) gene mutations (L29P and IVS9-1G>C). The same AIRE gene mutations can thus be associated with characteristic and noncharacteristic phenotypes of APS-1, and HLA may possibly influence the phenotype of APS-1. (C) 2002 Elsevier Science (USA).