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Twin DNA methylation profiling reveals flare-dependent interferon signature and B-cell promoter hypermethylation in systemic lupus erythematosus

ABSTRACT: Twin DNA methylation profiling reveals flare-dependent interferon signature and B-cell promoter hypermethylation in systemic lupus erythematosus

PROVIDER: PRJNA434098 | ENA |

REPOSITORIES: ENA

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Twin DNA methylation profiling reveals flare-dependent interferon signature and B-cell promoter hypermethylation in systemic lupus erythematosus

Project description:Objective: Systemic lupus erythematosus (SLE) has limited monozygotic (MZ) twin concordance, implying a role for other pathogenic factors than genetic variation, such as epigenetic changes. Using the disease discordant twin model, we investigated genome-wide DNA methylation changes in sorted CD4+ T-cells, monocytes, granulocytes and B-cells in twin pairs with at least one SLE-affected twin. Methods: Peripheral blood from 15 SLE twin pairs (six MZ, nine dizygotic (DZ)) was processed using gradient density centrifugation for the granulocyte fraction. CD4+ T-cells, monocytes and B-cells were further isolated using magnetic beads. Genome-wide DNA methylation was analysed using Infinium HumanMethylation450K BeadChips. Probes with a p-value <0.01 between SLE twins and co-twins were considered statistically significant and a median DNA methylation difference >7% biologically relevant. Findings were validated using pyrosequencing and replicated in an independent case-control sample. Results: In paired analyses of discordant SLE twins restricted to the gene promoter and start region, we identified 55, 327, 247 and 1628 genes with differentially methylated CpGs in CD4+ T-cells, monocytes, granulocytes and B-cells, respectively. All cell types displayed marked hypomethylation in interferon-regulated genes, such as IFI44L, PARP9 and IFITM1, which was more pronounced in twins with flare within the past two years. In contrast to the other cell types, differentially methylated CpGs in B-cells were predominantly hypermethylated, where the most important upstream regulators included TNF and EP300. Conclusion: Hypomethylation of interferon-regulated genes occurs in all major cellular compartments in SLE twins. The observed B-cell promoter hypermethylation is a novel finding with potential significance for SLE pathogenesis.

2018-03-19 | GSE110607 | GEO

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Gene expression analysis of skewed mouse T cells pre- vs post-injection, and ex vivo skin T cells from first disease vs flare, in a model of Cutaneous Lupus Erythematosus

Project description:We performed gene expression analysis on cultured Th0, Th1 and Th2 cells pre-injection, and on enriched T cells from lesional skin of cutaneous lupus erythematosus (CLE) mice post-injection, to compare differences in transcription that could predict skin tropism and flare

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Targeted protein expression analysis of skewed or drug-treated mouse T cells, and of serum from first disease vs flare in a model of Cutaneous Lupus Erythematosus

Project description:We performed targeted protein expression analysis on cultured Th0, Th1 and Th2 cells, and on T cells treated with known drug triggers of cutaneous lupus erythematosus (CLE). In tandem, we performed targeted protein expression analysis on serum from first vs flare Th2-injected mice in the CLE model.

2022-06-01 | GSE186095 | GEO

Spatial transcriptomics of Cutaneous and Systemic Lupus Erythematosus skin

Project description:We performed spatial transcriptomics on a case series of different clinical subtypes of cutaneous lupus erythematosus including acute cutaneous lupus erythematosus (malar rash, systemic lupus erythematosus). Our goals were to (1) determine which differentially expressed genes (DEGs) could be attributed to specific cell populations in specific locations within the tissue, (2) determine if spatial transcriptomics could better distinguish between CLE clinical subtypes than bulk RNA approaches and (3) examine potential cell-cell communication pathways within the skin lesions.

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Human peripheral blood cells: systemic lupus erythematosus vs healthy individual.

Project description:Gene expression profiling of peripheral blood cells from patients with systemic lupus erythematosus (SLE) vs healthy individual (HI).

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Gut microbiota in systemic lupus erythematosus

Project description:Gut microbiota in systemic lupus erythematosus

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High-Density Lipoproteins - small RNA Signatures in Systemic Erythematosus Lupus.

Project description:Study of high-density lipoproteins using 6 human plasma samples. The study sought to find small RNA signatures in systemic erythematosus lupus.

2018-10-27 | GSE121865 | GEO

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