ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2269

The Differences of DNA Methylome and Transcriptome Among Diverse Clinical Manifestations of Systemic Lupus Erythematosus

Ming Zhao1, Shuangyan Luo1, Honglong Wu2, Siyang Liu2, Meini Tang1, Wenjing Cheng1, Qing Zhang1, Xinhai Yu1, Tak Mao Chan3, Yudong Xia2, Na Yi2, Fei Gao2, Li Wang2, Ning Li2 and Qianjin Lu4, 1Department of Dermatology, Second Xiangya Hospital, Central South University; Hunan Key Laboratory of Medical Epigenomics, Changsha, China, 2Beijing Genomics Institute at Shenzhen, Shenzhen, China, Shenzhen, China, 3Division of Nephrology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China, 4Department of Dermatology, Second Xiangya Hospital, Central South University, Changsha, China

Meeting: 2012 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Systemic Lupus Erythematosus - Human Etiology and Pathogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Aberrant DNA methylation and gene expression have been observed in systemic lupus erythematosus (SLE). However, patterns of DNA methylation and gene expression associated with different clinical manifestations of SLE patients have never been reported.

Methods: DNA methylation was profiled by methylated DNA immunoprecipitation combined with high-throughput sequencing (MeDIP-seq) and the expression of genes was analyzed through transcriptome sequencing (transcriptome-seq) in CD4+T cells obtained from three groups [SLE with only skin lesion (S), SLE with skin lesion and renal disease (SK), Normal controls (N)] which constituted of four samples, respectively. Validations of DNA methylation status and expression levels of genes were performed with CD4+T cells from 15 samples from each group by bisulfite sequencing and MassArray and reverse transcription quantitative PCR (RT-qPCR), respectively.

Results: According to Different Methylated Regions (DMRs) in promoter regions of genomic DNA, we identified 3056 hypo-methylated and 1965 hyper-methylated genes in S group, and 4504 hypo-methylated and 1433 hyper-methylated genes in SK group, compared with controls. Several established autoimmune-associated genes (including ITGAM, IFI44, S1PR3 and NLRP2) were confirmed to be hypo-methylated in both S and SK groups by bisulfite sequencing and MassArray, consistent with results of MeDIP-seq. Gene Ontology (GO) analysis for ‘‘biological processes’’ showed a significant enrichment of 86 GO terms including “induction of apoptosis” and “response to UV” in genes with DMRs in S group. Similarly, apoptosis, adherens junction and leukocyte transendothelial migration were significantly enriched via KEGG pathway analysis. Moreover, 183 GO terms were enriched significantly in SK group, including “apoptosis” and “response to DNA damage stimulus”. KEGG pathway analysis revealed a significant enrichment of “renal cell carcinoma” and several autoimmune-associated pathways such as T cell receptor signaling pathway, MAPK signaling pathway and apoptosis. For differentially expressed genes, we observed 1500 up-regulated and 309 down-regulated genes in S group, and 944 up-regulated and 1552 down-regulated genes in SK group, compared with control. Over-expression of some genes including IFI44, ITGAM, S1PR3, NLRP2, C1QC and HLADRB was validated in S and SK groups using RT-qPCR, consistent with the results of transcriptome-seq. GO analysis showed that up-regulated genes were significantly enriched in immune-mediated processes including inflammation, leukocyte or complement activation. KEGG pathway analysis showed that “renal cell carcinoma” pathway was specifically enriched in down-regulated genes in SK group, suggesting aberrant DNA methylation and gene expression in this pathway may be related to lupus nephritis.

Conclusion: We characterized DNA methylome and transcriptome profiles in CD4+ T cells from SLE patients, and showed distinct patterns associated with different phenotypic disease manifestations.

Disclosure:

M. Zhao,
None;

S. Luo,
None;

H. Wu,
None;

S. Liu,
None;

M. Tang,
None;

W. Cheng,
None;

Q. Zhang,
None;

X. Yu,
None;

T. M. Chan,
None;

Y. Xia,
None;

N. Yi,
None;

F. Gao,
None;

L. Wang,
None;

N. Li,
None;

Q. Lu,
None.

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