Gene expression profiles of pediatric IBD remission patients
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ABSTRACT: Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation We performed (un)supervised clustering analysis of IBD-associated genes and applied Ingenuity® pathway software to identify specific molecular profiles between patients.
Project description:Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation We performed (un)supervised clustering analysis of IBD-associated genes and applied IngenuityM-BM-. pathway software to identify specific molecular profiles between patients. We analyzed RNA gene expression profiles of peripheral blood leucocytes (PBL) from pediatric IBD patients in clinical remission and age-matched controls.
Project description:Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have anti-oxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Mdr1a-/- mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet-gene interactions and potential effects of foods on remission or development of IBD. This study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a-/- mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0.2% curcumin or control + 0.1% rutin and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a-/- mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways probably mediated by PXR and PPARï¡ activation of RXR. These results reveal the potential of global gene expression and pathway analyses to study and better understand the effect of foods in colonic inflammation. Experiment Overall Design: Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0â¢2% curcumin or control + 0â¢1% rutin and monitored from the age of 7 to 24 weeks. As only curcumin significantly reduced colonic HIS, comparison of the gene expression levels in colon was carried out using total RNA from colon tissue of four mdr1a-/- mice from the control group (high HIS) and four mdr1a-/- mice from the curcumin group (low HIS). A reference design with eight arrays was used for this comparison, where each individual RNA sample was hybridized in the array with the reference RNA, totalizing 4 biological replicates per treatment.
Project description:To test the contribution of distinct ST-DC populations to either autoimmunity and inflammation or sustained disease remission, we evaluated the phenotypes of their blood precursors in a human model of disease flare following treatment withdrawal in RA patients in disease remission (the BioRRA study, (Baker et al., 2019)). We investigated the frequency and phenotype of PB DC2 and PB-DC3 of RA patients (n=12) in sustained clinical and ultrasound remission achieved with cDMARDs (Baker et al., 2019) by carrying out, and analysing single cell sequencing data at baseline remission levels, and upon endpoint after treatment withdrawal. We identified that PB DCs differ transcriptionally, but not proportionally, at the baseline of patients who sustain remission, versus those who go on to flare, and at endpoint. We propose that the transcriptomic profile of these peripheral blood DCs could be used as a biomarker of flare in remission RA patients.
Project description:Identify biomarkers to predict response to therapy in polyarticular juvenile idiopathic arthritis (JIA) using gene expression microarrays. 42 samples from 13 controls, 14 active patients, 9 patients in clinical remission with medication (CRM), and 6 patients in clinical remission without medication (CR). All patients had polyarticular JIA.
Project description:Damage of the intestinal epithelial barrier by xenobiotics or reactive oxygen species and a dysregulated immune response are both factors involved in the pathogenesis of inflammatory bowel diseases (IBD). Curcumin and rutin are polyphenolic compounds known to have anti-oxidant and anti-inflammatory activities, but their mechanism(s) of action are yet to be fully elucidated. Mdr1a-/- mice spontaneously develop intestinal inflammation, predominantly in the colon, with pathology similar to IBD, so this mouse model is relevant for studying diet-gene interactions and potential effects of foods on remission or development of IBD. This study tested whether the addition of curcumin or rutin to the diet would alleviate colonic inflammation in mdr1a-/- mice. Using whole-genome microarrays, the effect of dietary curcumin on gene expression in colon tissue was also investigated. Twelve mice were randomly assigned to each of three diets; control (AIN-76A), control + 0.2% curcumin or control + 0.1% rutin and monitored from the age of 7 to 24 weeks. Curcumin, but not rutin, significantly reduced histological signs of colonic inflammation in mdr1a-/- mice. Microarray and pathway analyses suggested that the effect of dietary curcumin on colon inflammation could be via an up-regulation of xenobiotic metabolism and a down-regulation of pro-inflammatory pathways probably mediated by PXR and PPARalpha activation of RXR. These results reveal the potential of global gene expression and pathway analyses to study and better understand the effect of foods in colonic inflammation. Keywords: Colonic inflammation, gene expression, curcumin, rutin, genome-wide microarrays
Project description:Treatment refractory Rheumatoid Arthritis (RA) is a major clinical challenge. Drug-free remission is uncommon but provides proof-of-concept that articular immune-homeostasis can be reinstated. In this project, we used single-cell RNA- to study the role of synovial tissue macrophages in maintaining disease remission. We have sequenced synovial tissue macrophages from individuals with healthy synovium (as evaluated by MRI), patients with undifferentiated arthritis (UPA), RA patients naïve to treatment, RA patients resistant to treatment and RA patients in disease remission
Project description:Remission has become both the gold standard for clinical care and the end point for clinical trials for children with juvenile idiopathic arthritis (JIA). Using gene expression microarrays, we found that when remission induced by methotrexate (MTX) or MTX plus a TNF inhibitor (etanercept, Et) (MTX+Et) was compared with healthy controls, there were notable differences in gene expression patterns, demonstrating that remission is not a restoration of immunologic normalcy. Differences were detected in PBMC as well as in granulocytes. Total RNA was extracted from isolated PBMC and granulocytes from patients with polyarticular JIA and from healthy controls. Patients had achieved remission (clinical remission on medicine as defined by Wallace et al, Arthritis Rheum. 2005;52(11):3354-3562) using either MTX or MTX+Et.
Project description:Immune-mediated inflammatory diseases (IMIDs) are typically characterised by relapsing and remitting flares of inflammation. However, the unpredictability of disease flares impedes their study. Addressing this critical knowledge gap, we used the experimental medicine approach of immunomodulatory drug withdrawal in rheumatoid arthritis (RA) remission to synchronise flare processes, allowing characterisation with unprecedented detail. We used single cell RNA sequencing to analyse the diversity and comparative longitudinal changes in paired circulating lymphocyte samples from 12 patients with RA in remission prior to drug cessation (on-drug remission) and after drug cessation (either off drug flare, or drug-free remission) as part of the Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study.
Project description:Renal infiltration with mononuclear cells is associated with poor prognosis in SLE. A renal macrophage/dendritic cell signature is associated with onset of nephritis in NZB/W mice and immune modulating therapies can reverse this signature and the associated renal damage despite ongoing immune complex deposition. Our findings suggest that mononuclear phagocytes with an aberrant activation profile contribute to tissue damage in lupus nephritis by mediating both local inflammation and excessive tissue remodeling. We used microarrays to analyze the gene expression of renal isolated macrophages at early stage of lupus (young) during lupus nephritis (sick) and after induction of remission (Rem) NZB/W F4/80hi mouse cells were isolated using flow cytometry; RNA from cells (young, sick and after complete remission) was extracted and processed for hybridization on Affymetrix microarrays.