Molecular Signatures in Skin Associated with Clinical Improvement During Mycophenolate Treatment in Systemic Sclerosis
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE45485 | GEO | 2013/04/09
SECONDARY ACCESSION(S): PRJNA196637
REPOSITORIES: GEO
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Project description:Skin gene expression signatures, including intrinsic subset, are associated with skin score/MRSS improvement during mycophenolate mofetil (MMF) treatment. Gene expression and intrinsic subset assignment were measured in SSc patients amd controls at baseline, and from biopsies of MMF-treated patients.
2013-04-09 | E-GEOD-45485 | biostudies-arrayexpress
Project description:Skin gene expression signatures, including intrinsic subset, are associated with improvement during Mycophenolate mofetil (MMF) treatment.
2014-07-25 | GSE59785 | GEO
Project description:Background: Only a subset of patients with systemic sclerosis (SSc) demonstrate improvement in modified Rodnan skin score (mRSS) during mycophenolate mofetil (MMF) treatment. Here we investigated the molecular and cellular effects in skin associated with MMF therapy in subjects who demonstrated or lacked clinical improvement. Methods: Clinical and skin gene expression data were obtained genome-wide from baseline and longitudinal (6-, 12-, 24-, and 36-mo) biopsies in 33 MMF-treated subjects with SSc. Clinical improvement was defined as mRSS reduction ≥ 25%. An inflammatory signature score was calculated for each patient sample using single-sample gene set enrichment analysis (ssGSEA). Cell type specific changes during treatment were characterized. Results: Eleven subjects with SSc completed at least 24 months of MMF therapy and were termed ‘completers’. Two distinct gene expression patterns were observed that corresponded to MMF treatment status. Three subjects showed attenuation of the inflammatory signature by 24 months, paralleling reductions in activated dendritic cells. MMF cessation at 24 months resulted in an inflammatory signature rebound paralleling mRSS increase. Three subjects that remained on MMF showed persistent inflammatory signature reductions with decreasing or stable mRSS. The remaining six completers either did not fulfill minimum mRSS (n=5), and/or lacked a baseline inflammatory signature (n=4). Conclusions: An elevated inflammatory skin gene expression signature is associated with clinical improvement during MMF therapy. Inflammation returned upon MMF discontinuation with concomitant mRSS increase. These data summarize MMF’s molecular effects in skin and support MMF therapy for longer than 24 months in patients who demonstrate clinical response.
2017-01-01 | GSE76885 | GEO
Project description:Skin gene expression signatures, including intrinsic subset, are associated with improvement during Mycophenolate mofetil (MMF) treatment. Longitudinal SSc patient biopsies and controls were integrated into 83 sample dataset totaling 165 arrays for gene expression and analysis
2014-07-25 | E-GEOD-59785 | biostudies-arrayexpress
Project description:PBC RNA samples from 134 baseline and 98 month-12 visits, corresponding to the active treatment period of both arms in Scleroderma Lung Study II, along with 45 healthy controls were investigated by global RNA sequencing. The objective was to examine the peripheral blood cell (PBC) gene expression changes ensuing from mycophenolate mofetil (MMF) or cyclophosphamide (CYC) treatment and to determine the predictive significance of baseline PBC transcript scores for response to immunosuppression in systemic sclerosis (SSc) related interstitial lung disease (ILD).
2022-02-01 | GSE181228 | GEO
Project description:This study was conducted in order to assess the effects of the compound Mycophenolate mofetil (MMF), an inhibitor of the enzyme inosine monophosphate dehydroxygenase (IMPDH) with a strong cytostatic effect on T-cells, on the phenotype of human carotid artery stenosis in humans in vivo. This was done at the transcriptome level by comparing the gene expression profiles of carotid endarterectomy samples from patients with carotid artery stenosis (>70% diameter stenosis on angiography) that were randomly assigned to treatment with MMF 1000 mg (N=9) or Placebo (N=11), respectively. MMF or placebo was given for at least 2 weeks prior to undergoing carotid endarterectomy (CEA).
2009-02-01 | GSE13922 | GEO
Project description:Lupus nephritis (LN) is one of the more severe systemic lupus erythematosus manifestations with the potential of developing into end stage kidney disease. Mycophenolate mofetil (MMF) and Azathioprine (AZA) are widely used for both induction and maintenance therapy for LN, but the one year complete renal response ranges from 30-40% in most trials. Reasons for non-response are still unknown. Thus, anticipating lack of drug efficacy in a patient could lead to early introduction of advanced therapies. A longitudinal cohort comprising gene-expression and clinical data of responder and non-responder samples to MMF, AZA and standar of care drugs (hidroxicloroquine (HC) and HC + glococorticoids (GC) (SOC)) was retrospectively analyzed. Response to drugs was defined over time using SRI-4 scores. Differential gene expression and functional analysis were performed. Response rate was measured based on blood cell proportions. Single-cell RNA sequencing data was analyzed to identify the cell subtypes influencing non-response and their contributing genes. SLE: Systemic Lupus Erythematosus; MMF: Mycophenolate mofetil; AZA: Azathioprine; HC: Hydroxychloroquine; PHC: Prednisone (Glucocorticoid (GC)) + HC; SOC: Standard Of Care drugs (HC and HC + PHC)
2023-05-01 | GSE224705 | GEO
Project description:Mycophenolate mofetil (MMF) has been widely prescribed for neuromyelitis optica spectrum disorders (NMOSD) although some patients experience severe gastrointestinal (GI) side effects following MMF administration. Our study investigated the potential mechanisms of this toxicity in NMOSD patients. We constructed MMF-induced colitis mouse model and produced a multi-omic dataset in which microbiome and metabolome analysis from the mouse GI tract to decipher the mechanisms of MMF GI toxicity. Further, 17 female NMOSD patients treated with MMF were prospectively enrolled and grouped according to the diarrhea symptom as non-diarrhea NMOSD group (NM) and diarrhea NMOSD group (DNM) as well as healthy controls (HC, 12 female). The gut microbiota was analyzed using 16S rRNA sequencing of stool samples. In the mouse model, we found that vancomycin administration drastically altered the colon content metabolomes and microbiomes and prevented MMF-induced body weight loss, cecal and colon tissue injury. Bacteroidetes and Firmicutes converted phenyl-beta-D-glucuronide (MPAG) to mycophenolic acid (MPA) that could result in damaged intestinal tissue. We also demonstrated that the alpha diversity in the DNM group was increased and this was accompanied by increased Firmicutes and Proteobacteria abundance. Collectively, these results reveal that alterations of the gut microbiome and metabolome contribute to MMF-induced colitis. Modifying of the gut microbiome and metabolome may alleviate MMF-induced GI toxicity in NMOSD patients.
2024-06-18 | MTBLS4392 | MetaboLights
Project description:The efficacy of abatacept in patients with early diffuse systemic sclerosis (dcSSc) was analyzed to test the hypothesis that patients in the inflammatory intrinsic gene expression subset would show the most significant clinical improvement. 84 participants with dcSSc were randomized to receive abatacept or placebo for 12 months. RNA-seq was performed on 233 skin paired biopsies at baseline, 3- and 6-months. Improvement was defined as a 5 point or >20% change in modified Rodnan skin score (mRSS) between baseline and 12 months. Samples were assigned to intrinsic gene expression subset (inflammatory, fibroproliferative, or normal-like). In the abatacept arm, change in mRSS was most pronounced for the inflammatory (p<0.001) and normal-like (p=0.03) subsets relative to placebo. Participants on placebo remained in their molecular subset while inflammatory participants treated with abatacept moved toward normal-like. The CD28 costimulation pathway decreased in patients that improved on abatacept (FDR=5.88x10-4) and was specific to the inflammatory subset (FDR=0%). Patients in the inflammatory subset had elevation of the CD28 costimulation pathway at baseline relative to fibroproliferative (p = 0.0026) and normal-like (p=0.0001) participants. There was a correlation between improved ΔmRSS and baseline expression of the CD28 costimulation pathway (R=-0.62, p=0.02). This study provides an example of precision medicine in SSc clinical trials.
2023-02-01 | GSE217067 | GEO
Project description:Systemic sclerosis skin disease trajectory during mycophenolate mofetil treatment
| PRJNA308851 | ENA