Project description:Post-translational modifications (PTMs) are considered to be an important factor in the pathogenesis of SLE. Lysine 2-hydroxyisobutyryl (Khib), as an emerging post-translational modification of proteins, is involved in some important biological metabolic activities. We compared the Khib levels of SLE patients and healthy controls based on liquid chromatography-tandem mass spectrometry, and then performed proteomic analysis. The results showed that Khib in SLE patients was up-regulated at 865 sites of 416 proteins and down-regulated at 630 sites of 349 proteins. The site abundance, distribution and function of Khib protein were further analyzed. Bioinformatics analysis showed that complement, coagulation cascade and platelet activation in immune-related pathways were significantly enriched, indicating that the differential modification proteins between them might affect SLE.
Project description:Systemic lupus erythematosus (SLE), also known simply as lupus, is an autoimmune disease. There is no cure for SLE. The mechanism involves an immune response by autoantibodies against a person's own tissues. However, the mechanism underlying imbalance of autoantibodies is not clear. In this experiment, peripheral blood was obtained from normal healthy donors and systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells (PBMC) were separated by Ficoll separation solution. Samples of four (total eight) donors were pooled and Samples of four (total eight) SLE patients were pooled. The aim was to characterize the mRNA profile of SLE patients compared to healthy donors and find the new target of diagnosis or treatment for SLE.
Project description:Epigenetic alternations in addition to genetic factors are important contributors to the pathogenesis of Systemic Lupus Erythematosus (SLE). Recent studies revealed that aberrant changes in DNA methylation occur in SLE patients, and potentially contributes to the pathogenesis. Using genome-wide DNA methylation microarray, the Illumina Infinium HumanMethylation450 BeadChip, we compared the DNA methylation level of white blood cells between Chinese female SLE patients with that of healthy controls. There was no difference in global levels of DNA methylation between SLE patients and controls. However, we identified 36 CpG sites with differential loss of DNA methylation and 8 CpG sites with differential gain of DNA methylation, representing 26 genes and 7 genes respectively. Surprisingly, nearly half of the hypomethylated CpG sites were located in the CpG shores, which implicated the functional importance of loss of DNA methylation in the CpG shores in SLE.
2016-12-21 | GSE76056 | GEO
Project description:microbiome in different body sites in SLE patients
Project description:To screen the differentially expressed lncRNAs, we performed lncRNA profiling using ArrayStar Human LncRNA Microarray in 24 new-onset systemic lupus erythematosus (SLE) patients and 12 age- and sex-matched healthy controls (HCs). For the lncRNA microarray screening, total RNA from plasma was isolated from 12 SLE without nephritis, 12 lupus nephritis (LN) and 12 HCs. Four RNA samples were mixed togther as a pool of sample for microarray analysis. Accordingly, there were each three pooled RNA samples from 12 SLE without nephritis, 12 LN and 12 HCs for microarray analysis. Hierarchical clustering showed the plasma levels of lncRNAs and mRNAs differed significantly between 24 new-onset SLE patients and 12 control subjects. With a fold change ≥ 2 and P ≤ 0.05, we identified 1315 significantly differentially expressed lncRNAs (743 lncRNAs up-regulated and 572 lncRNAs down-regulated) and 1363 differentially expressed mRNAs (745 mRNAs up-regulated and 618 mRNAs down-regulated) in plasma of SLE patients compared with control samples.
Project description: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.
Project description:Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects multiple organs. Protein lysine modifications play important roles in gene regulation, transcription, metabolism and other biological processes. The lysine 2-hydroxyisobutyrylation(Khib) histone mark has recently been discovered as a novel protein modification. Utilizing antibody-based affinity enrichment and nano-HPLC/MS/MS analyses of Khib peptides, we identified 156 upregulated proteins(fold change>1.5),124 downregulated proteins(fold change<1/1.5), including 220 Khib sites that were upregulated and 187 Khib sites that were downregulated. Our data demonstrate that proteins with Khib sites were localized in the cytoplasm. Functional enrichment analysis revealed that proteins with Khib sites are broadly involved in a wide range of biological processes, cellular components and molecular functions. The 03010 Ribosome pathways may exert important influence on the SLE pathogenic mechanism, according to a KEGG analysis. The functional analysis of Khib is of value for important future investigations of SLE pathogenesis.
Project description:Background Systemic lupus erythematosus (SLE) is a severe systemic autoimmune disease with multiple manifestations. Lysine crotonylation (Kcr) is a newly discovered post-translational modification (PTM) epigenetic pattern which may affect gene expression and linked to diseases causally. Methods We collected blood samples from 11 SLE individuals and 36 healthy subjects. Then we used highly sensitive liquid chromatography-mass spectrometry technology to carry out proteomics and quantitative crotonylome analysis of SLE peripheral blood mononuclear cells in this investigation, which indicated the unique etiology of SLE. Results There were 618 differentially expressed proteins (DEPs), and 612 crotonylated lysine sites for 272 differentially modified proteins (DMPs) found. According to KEGG analysis and ingenuity pathway analysis, these DEPs and DMPs are primarily enriched in the leukocyte extravasation signaling pathway. Conclusions This is the first study of crotonylated modification proteomics in SLE. The leukocyte extravasation signaling pathway had a considerable concentration of DEPs and DMPs, indicating that this pathway may be involved in the pathogenic development of SLE.
Project description:Methyl-seq data was obtained from total peripheral blood mononuclear cells of two patients with systemic lupus erythematosus who were characterized as having>2 standard deviations more ARID3a-expressing B lymphocytes than healthy controls. Similarly, methyl-seq data was also obtained from two SLE patient samples with normal (low) numbers of ARID3-expressing B lymphocytes. Our previous studies showed that increased ARID3a expression in B lymphocytes was associated increased disease activity. Data were generated on an Illumina Hiseq 2000 with paired-end 100bp reads and quality control metrics were assessed with Picard tools. Methylation profiles of genomic DNA from four SLE patient PBMC samples, two with high numbers of ARID3a expressing B cells (ARID3aH) versus two with normal numbers of ARID3a+ B cells (ARID3aN), were generated on an Illumina Hiseq 2000 with paired-end 100bp reads.