AIRE hypoexpression and transcriptome profiles correlate with thymic impairment in Down syndrome
Transcriptomics Dataset
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General Information
AccessionGSE23910
TitleAIRE hypoexpression and transcriptome profiles correlate with thymic impairment in Down syndrome
DescriptionDown syndrome (DS) patients frequently develop organ-specific autoimmune disorders, particularly endocrinopathies and coeliac disease, as well as an increased susceptibility to mucosal candidiasis. These clinical features resemble APECED (autoimmune-polyendocrinopathy-candidiasis-ectodermal-dystrophy), a monogenic condition due to mutations in the AIRE gene, located on 21q22.3 and already described as down-regulated in 21 trisomy. Here we investigated AIRE expression and global gene expression profiles in surgically removed thymuses from 14 DS infants and children with congenital heart defects and from 42 age-matched individuals with cardiac defect as an isolated malformation. Immunohistochemistry revealed significantly reduced AIRE expression in DS thymuses (70.4849.59 positive cells/mm2 in DS X 154.7061.16 in controls, p<0.0001). qPCR confirmed the lower expression of AIRE in DS thymuses. Global thymic RNA profiles from DS patients and controls revealed 407 genes significantly hypoexpressed in DS. Network transcriptional analysis showed that hypoexpressed genes are related to biological processes such as antigen processing and presentation of endogenous antigen (ERAP2, CD1D), negative (PRDX2) and positive (CD3D, CD74) thymic T-cell selection and homeostasis of number of cells (PRDX2). Altogether these findings may explain the high prevalence of autoimmune phenomena in DS patients. Moreover, our data are in accordance with previous findings of thymic abnormal development in DS patients, characterized by lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation. Global gene profiles indicate that in DS patients, the trisomic imbalance probably leads to thymic hypofunction. In conclusion, lower AIRE expression and the impairment of other crucial pathways for central tolerance could well explain the high prevalence of organ-specific autoimmune disorders in DS.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23910
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
Keyword
Dataset Accession
Enrichr
Published May 2016
A comprehensive gene set enrichment analysis web server 2016 update
7759
65
Characteristic Direction
Published March 2014
A geometrical multivariate approach to identify differentially expressed genes
26829
GeneMANIA
Published June 2010
Biological network integration for gene prioritization and predicting gene function
7435
L1000CDS2
Published August 2016
An ultra-fast LINCS L1000 Characteristic Direction signature search engine
7756
PAEA
Published November 2015
Enrichment analysis tool implementing the principal angle method
3879
Canned Analyses generated with the dataset
Filters  
Dataset Accession
Tool Name
Direction
Geneset
Interaction network and enrichment analysis of genes downregulated in Down syndrome
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Interaction network and enrichment analysis of genes upregulated in Down syndrome
GeneMANIA, Characteristic Direction
The analysis explores the gene interaction network and pathway enrichment of the top 50 mo...
Small molecules which mimic Down syndrome
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which mim...
Small molecules which reverse Down syndrome
L1000CDS2, Characteristic Direction
The L1000 database was queried in order to identify small molecule perturbations which rev...
Enrichment analysis of genes dysregulated in Down syndrome
PAEA, Characteristic Direction
An enrichment analysis was performed on the top most dyresgulated genes determined by appl...
Enrichment analysis of genes downregulated in Down syndrome
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most downregulated genes identified by...
Enrichment analysis of genes upregulated in Down syndrome
Enrichr, Characteristic Direction
An enrichment analysis was performed on the top 500 most upregulated genes identified by a...
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