Project description:Genome-wide analysis of DNA methylation profiles from patients with Sjögren's syndrome with high versus low fatigue levels using the Illumina Infinium HumanMethylation450 Beadchip array. Background Chronic fatigue is a common, disabling, and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary Sjögren’s syndrome (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods 48 pSS patients with high (n=24) or low (n=24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array.
Project description:Investigating differential gene expression between clinical phenotypes in primary Sjögren's Syndrome using matched healthy controls as a further comparator group. Samples are derived from the UK Primary Sjögren's Syndrome Registry (UKPSSR)
Project description:One of the most important advantages of mass spectrometry is the ability to quantify proteins and their modifications in parallel to obtain a holistic picture of the protein of interest. Here, we present a hybrid immunoaffinity targeted mass spectrometry (MS) approach that combines efficient pan-antibody enrichment of a specific protein from plasma with the selectivity of targeted MS analysis to quantitate specific protein modifications. In this study, we used this approach to quantify plasma levels of the chemokine CXCL10 that has been associated with many immunological disorders such as systemic lupus erythematosus and primary Sjögren's Syndrome. The hybrid approach enabled sensitive, specific and simultaneous quantification of total, full-length (active) CXCL101-77 and DPP4 truncated (inactive) CXCL103-77 in human plasma. Samples from 30 healthy individuals and 34 primary Sjögren's Syndrome patients were analyzed. The ratio of CXCL101-77 to truncated CXCL103-77 was significantly increased and demonstrated an improved classification of the primary Sjögren's syndrome patients (ROC AUC = 0.74) when compared to total CXCL10 (ROC AUC = 0.66). Furthermore, the ratio of CXCL101-77 to truncated CXCL103-77 correlated best with Sjögren's syndrome disease activity. As this strategy can be readily adapted to other proteins and modifications of interest, we are convinced that it will lead to a more detailed understanding of different proteoforms in physiology and pathology yielding more relevant biomarkers and drug targets.
Project description:We compared subsets of B cells as follows: Bm1 cells; CD38-IgD+, naïve B cells; CD38+IgD+, pre-germinal centre B cells; CD38highIgD+ and memory B cells; CD38±IgD that were collected from patients with primary Sjögren's syndrome. As a result, list of 623 differentially expressed genes was created. We found interferon signature genes and HLA genes were mostly up-regulated in patients compared to healthy controls.
Project description:Genome-wide analysis of DNA methylation profiles from patients with Sjögren's syndrome with high versus low fatigue levels using the Illumina Infinium HumanMethylation450 Beadchip array. Background Chronic fatigue is a common, disabling, and poorly understood phenomenon. Recent studies indicate that epigenetic mechanisms may be involved in the expression of fatigue, a prominent feature of primary Sjögrenâs syndrome (pSS). The aim of this study was to investigate whether DNA methylation profiles of whole blood are associated with fatigue in patients with pSS. Methods 48 pSS patients with high (n=24) or low (n=24) fatigue as measured by a visual analogue scale were included. Genome-wide DNA methylation was investigated using the Illumina HumanMethylation450 BeadChip array. Case-case study including Sjögren's patients with high fatigue (n=24) and patients with low fatigue levels (n=24)
Project description:Fatigue is a debilitating condition with a significant impact on patientsâ quality of life. Fatigue is frequently reported by patients suffering from primary Sjo Ìgrenâs Syndrome (pSS), a chronic autoimmune condition characterised by dryness of the eyes and the mouth. However, although fatigue is common in pSS, it does not manifest in all sufferers, providing an excellent model with which to explore the potential underpinning biological mechanisms. Whole blood samples from 131 fully-phenotyped pSS patients, stratified for the presence of fatigue, collected by the UK primary Sj Ìogrenâs Syndrome Registry were used for whole genome microarray. The resulting data were analysed both on a gene by gene basis and using pre-defined groups of genes. Finally, gene set enrichment analysis (GSEA) was used as a feature selection technique for input into a support vector machine (SVM) classifier. Classification was assessed using area under curve (AUC) of receiver operator characteristic and standard error of Wilcoxon statistic, SE(W). Contributor: The UK Primary Sjögrenâs syndrome registry