Transcriptomic Segregation of Human Autoantigens Useful for the Diagnosis of Autoimmune Diseases.
Transcriptomic Segregation of Human Autoantigens Useful for the Diagnosis of Autoimmune Diseases.
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DOI：
10.1007/s40291-016-0211-6
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发表时间：
2016-10
影响因子：
4
通讯作者：
Sapio MR
中科院分区：
文献类型：
--
作者：
Burbelo PD;Iadarola MJ;Alevizos I;Sapio MR
在自身免疫患者的临床护理中，自身抗体的测量可以进行诊断、监测，甚至可以预测疾病。尽管自身抗体靶蛋白具有临床应用价值，但其在许多自身免疫性疾病中的功能意义仍不清楚。在这里，我们提出了一个全面的回顾52个自身抗原，通常用于血清学诊断的24种自身免疫性疾病。我们讨论了它们的功能，它们是否有细胞外暴露的表位，以及这些蛋白质的抗体是否已知是致病的。利用转录组学(RNA-Seq)数据集显示32个组织和器官中自身抗原的信使RNA(MRNA)表达。分析表明，自身抗原可分为三组：在疾病影响最严重的组织中表达(第一组)，在免疫组织中普遍表达并丰富(第二组)，或在其他与临床表现不典型相关的组织中表达(第三组)。聚类分析表明，组I中的自身抗原通常是含有胞外表位的蛋白质，其中许多表位是致病自身抗体的靶标。第二组自身抗原是几种风湿性疾病的靶标，包括干燥综合征、系统性红斑狼疮、肌炎和系统性硬化症，在免疫丰富的组织中普遍表达。这增加了第二组疾病中的免疫细胞可能是自身免疫的来源和/或免疫细胞反应的目标的可能性。由于自身抗原基因表达丰富的组织可能有助于自身抗体的发展和随后的自身免疫，从自身抗原转录图谱中产生的新模式可能提供一个新的启发式框架来解开这些复杂的疾病。
The measurement of autoantibodies in the clinical care of autoimmune patients allows for diagnosis, monitoring, and even disease prediction. Despite their clinical utility, the functional significance of autoantibody target proteins in many autoimmune diseases remains unclear. Here we present a comprehensive review of 52 autoantigens commonly employed for the serological diagnosis of 24 autoimmune diseases. We discuss their function, whether they have extracellular-exposed epitopes, and whether antibodies to these proteins are known to be pathogenic. Transcriptomics (RNA-Seq) datasets were mined to display messenger RNA (mRNA) expression of the autoantigens across 32 tissues and organs. This analysis revealed that autoantigens cluster into one of three groups: expression in the tissue most strongly affected in the disease (Group I), ubiquitous expression with enrichment in immune tissues (Group II), or expression in other tissues not typically associated with the clinical presentation (Group III). Clustering demonstrated that the autoantigens within Group I were often proteins containing extracellular epitopes, many of which are targets of pathogenic autoantibodies. Group II autoantigens were targets for several rheumatological diseases, including Sjögren syndrome, systemic lupus erythematosus, myositis, and systemic sclerosis, and were ubiquitously expressed with enrichment in immune-rich tissues. This raises the possibility that immune cells in Group II disorders may be the source of autoimmunization and/or targets of immune cell responses. Since tissues showing enriched autoantigen gene expression may contribute to the development of autoantibodies and subsequent autoimmunity, the emergent patterns arising from the autoantigen transcriptomic profiles may provide a new heuristic framework to deconvolute these complex disorders.
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影响因子：
158.5
作者：
Arbuckle, MR;McClain, MT;Harley, JB
通讯作者：
Harley, JB
影响因子：
13.6
作者：
Burbelo, Peter D.;Arnbatipudi, Kiran;Alevizos, Ilias
通讯作者：
Alevizos, Ilias
DOI：
10.1038/ncprheum0895
发表时间：
2008-09
期刊：
NATURE CLINICAL PRACTICE RHEUMATOLOGY
影响因子：
--
作者：
Elkon, Keith;Casali, Paolo
通讯作者：
Casali, Paolo
影响因子：
3.5
作者：
Crow, MK;Kirou, KA;Wohlgemuth, J
通讯作者：
Wohlgemuth, J
影响因子：
168.9
作者：
Atkinson, Mark A.;Eisenbarth, George S.;Michels, Aaron W.
通讯作者：
Michels, Aaron W.