Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1.
Proteome-wide survey of the autoimmune target repertoire in autoimmune polyendocrine syndrome type 1.
复制标题
DOI：
10.1038/srep20104
复制
发表时间：
2016-02-01
影响因子：
4.6
通讯作者：
Kämpe O
中科院分区：
文献类型：
--
作者：
Landegren N;Sharon D;Freyhult E;Hallgren Å;Eriksson D;Edqvist PH;Bensing S;Wahlberg J;Nelson LM;Gustafsson J;Husebye ES;Anderson MS;Snyder M;Kämpe O
自身免疫性多内分泌综合征1型（APS1）是一种单基因疾病，具有多种自身免疫性疾病的表现。它是由自身免疫调节因子（AIRE）基因突变引起的，AIRE基因在建立中枢免疫耐受的关键过程中促进了数千种外周组织抗原的胸腺展示。我们在这里使用蛋白质组阵列进行全面的研究APS 1中的自身免疫靶点。对已建立的自身抗原的询问揭示了自身抗体的高度可靠的检测，并且通过探索超过9000种蛋白质的完整组，我们进一步鉴定了MAGEB 2和PDILT为APS 1中的新型主要自身抗原。我们的蛋白质组范围的评估揭示了组织特异性免疫靶点的显著富集，反映了AIRE对这类基因的选择性。我们的研究结果还表明，在APS 1中，只有非常有限的一部分蛋白质组成为免疫系统的目标，这与与AIRE缺陷相关的胸腺呈递的广泛缺陷形成对比，并提出了新的问题，需要哪些其他因素来打破耐受性。
Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE’s selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.