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Series GSE118144 Query DataSets for GSE118144
Status Public on Feb 19, 2019
Title Cell lineage-specific genome-wide DNA methylation analysis of patients with paediatric-onset systemic lupus erythematosus
Organism Homo sapiens
Experiment type Methylation profiling by genome tiling array
Summary Background: Patients with paediatric-onset systemic lupus erythematosus (SLE) often present with more severe clinical courses than adult-onset patients. Although genome-wide DNA methylation (DNAm) profiling has been performed in adult-onset SLE patients, parallel data on paediatric-onset SLE are not available. Therefore, we undertook a genome-wide DNAm study in paediatric-onset SLE patients across multiple blood cell lineages.
Methods: The DNAm profiles of four purified immune cell lineages were compared in 16 Chinese patients with paediatric-onset SLE and 13 healthy controls using the Illumina HumanMethylationEPIC BeadChip. The DNAm dataset consisted of 145 samples, including data from CD4+ T cells, CD8+ T cells, B cells, neutrophils and whole blood.
Results: Genome-wide DNAm analysis revealed considerable variation in DNAm levels across samples, and as expected, clustering occurred by cell type rather than disease status. Comparison of DNAm in whole blood and within each independent cell lineage identified a consistent pattern of loss of DNAm at 21 CpG sites overlapping 15 genes, which represented a robust, disease-specific DNAm signature for paediatric-onset SLE in our cohort. This DNAm signature shows considerable overlap with that identified in our adult-onset SLE patient cohort, predominantly showing a loss of DNAm and enrichment in genes involved in type I interferon signalling in SLE, regardless of the age of onset. In addition, cell lineage-specific changes, involving both loss and gain of DNAm, were observed in both novel genes and genes with well-described roles in SLE pathogenesis.
Conclusion: The SLE-specific DNAm signature has the potential to develop into a diagnostic biomarker for SLE, which is particularly important for paediatric-onset patients, as diagnosing SLE in children can be challenging. This study also highlights the importance of studying DNAm changes in different immune cell lineages rather than only whole blood, since cell type-specific DNAm changes facilitated the elucidation of the cell type-specific molecular pathophysiology of SLE.
Overall design DNA was extracted from whole blood and four purified lineages (CD4+ T cells, CD8+ T cells, CD19+ B cells and CD16+ neutrohils) from each participant. The DNA methylation data of 16 SLE was compared with 13 ethnic-matched healthy controls. All the patients are self-reported to be Chinese and all met the criteria of the American College of Rheumatology for SLE diagnosis. Genomic DNA was bisulfite converted and DNA methylation was measured by Illumina MethylationEPIC BeadChip.
Contributor(s) Yeung KS, Lee TL, Mok MY, YuMak C, Yang W, Chong CY, Lee PW, Ho HK, Choufani S, Lau CS, Lau YL, Weksberg R, Chung HY
Citation(s) 30806140
Submission date Aug 06, 2018
Last update date Mar 18, 2019
Contact name Brian Chung
Organization name The University of Hong Kong
Department Paediatrics and Adolescent Medicine
Street address 102 Pokfulam Road
City Hong Kong
State/province Hong Kong
ZIP/Postal code 852
Country Hong Kong
Platforms (1)
GPL21145 Infinium MethylationEPIC
Samples (145)
GSM3319359 SLE020_9B: SLE patient_purified B cells
GSM3319360 BUC015_WB: Control_whole blood
GSM3319361 BUC019_9B: Control_purified CD19+ B cells
BioProject PRJNA484705

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE118144_Normalized_data.txt.gz 1.6 Gb (ftp)(http) TXT
GSE118144_RAW.tar 2.1 Gb (http)(custom) TAR (of IDAT)
Raw data provided as supplementary file
Processed data are available on Series record

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