Dupilumab therapy-associated conjunctivitis and the Ocular Surface Miorobiome
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PROVIDER: PRJEB56082 | ENA |
REPOSITORIES: ENA
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Project description:Ocular surface microbiome in dupilumab associated ocular surface disease
| PRJEB57775 | ENA
Project description:The major focus of Dr. Argueso's research is to characterize the carbohydrate portion of the different mucins expressed by the ocular surface epithelia as well as the enzymes involved with their synthesis, and to determine whether the alteration of mucin glycosylation is associated with ocular surface disease. Highly glycosylated mucins on the ocular surface (cornea and conjunctiva) are the first line of defense of the eye against injury and infection. Changes in O-glycosylation of mucins may cause ocular surface disorders, such as dry eye. Gene expression patterns in the conjunctival epithelium of three normal subjects were analyzed. The three subjects have the same ABO-blood-group. For each donor, conjunctival cells were obtained by impression cytology. Conjunctival impression cytology was performed on each eye two times with a one-week interval. Conjunctival cells obtained from each individual were pooled and the RNA isolated. All three samples were hybridized to the custom designed CFG GLYCOv2 glycogene array.
2011-03-02 | E-GEOD-27593 | biostudies-arrayexpress
Project description:The major focus of Dr. Argueso's research is to characterize the carbohydrate portion of the different mucins expressed by the ocular surface epithelia as well as the enzymes involved with their synthesis, and to determine whether the alteration of mucin glycosylation is associated with ocular surface disease.
2011-03-02 | GSE27593 | GEO
Project description:Recently we had discovered a solid cord like structure at the limbus of human eyes, termed as the Limbal Epithelial Crypt (LEC). It arises from the undersurface of the interpalisade rete ridges and extends towards the conjunctiva over the conjunctival stroma. Anatomical and immunohistochemical studies have shown it to be potentially a Stem Cell Niche. To confirm this hypothesis we conducted comparative gene expression profile of LEC with pathway and Geneontology studies in comparison with other ocular surface epithelial regions such as cornea, limbus, LEC stroma and conjunctiva. Frozen tissue blocks of corneoscleral buttons dissected from cadaver eyes were cryosectioned. These tissue sections from different ocular surface regions were laser microdissected. Extracted RNA was amplified & hybridized to 30,000k Human spotted cDNA microarray chips. Raw data obtained with Genepix Pro6 software was filtered, normalized & analysed on BASE & Jexpresspro software. Unpaired T-Test, Significance Analysis of Microarrays were performed on the data. Database for Annotation, Visualisation, and Integrated Discovery (DAVID) (http://www.DAVID.niaid.nih.gov) and Ingenuity Pathway Analysis (IPA) was used to determine the enriched GO terms and pathways in the differentially expressed genes. Quantitative gene expression analysis (qPCR) and immunohistochemistry was performed on the genes of interest. Statistical analysis for real time PCR was performed on SPSS16 to determine the normalised expression of gene of interest on ocular surface regions. Samples were prepared from five human ocular surface epithelial regions such as Cornea, Limbus, LEC, LEC Stroma, Conjunctiva. There were four replicates in each groups except Cornea and Conjunctiva with 3 each. The Standard Probe (SP) was prepared from mixing equal amount of Corneal and conjunctival epithelial RNA followed by ethanol precipitation. Samples were labelled with Cy5 dye and Standard Probe with Cy3 Dye. These were mixed in equal amount to prepare hybrid probes which were then hybridised to microarray slide.
2010-03-23 | E-GEOD-19035 | biostudies-arrayexpress
Project description:Recently we had discovered a solid cord like structure at the limbus of human eyes, termed as the Limbal Epithelial Crypt (LEC). It arises from the undersurface of the interpalisade rete ridges and extends towards the conjunctiva over the conjunctival stroma. Anatomical and immunohistochemical studies have shown it to be potentially a Stem Cell Niche. To confirm this hypothesis we conducted comparative gene expression profile of LEC with pathway and Geneontology studies in comparison with other ocular surface epithelial regions such as cornea, limbus, LEC stroma and conjunctiva. Frozen tissue blocks of corneoscleral buttons dissected from cadaver eyes were cryosectioned. These tissue sections from different ocular surface regions were laser microdissected. Extracted RNA was amplified & hybridized to 30,000k Human spotted cDNA microarray chips. Raw data obtained with Genepix Pro6 software was filtered, normalized & analysed on BASE & Jexpresspro software. Unpaired T-Test, Significance Analysis of Microarrays were performed on the data. Database for Annotation, Visualisation, and Integrated Discovery (DAVID) (http://www.DAVID.niaid.nih.gov) and Ingenuity Pathway Analysis (IPA) was used to determine the enriched GO terms and pathways in the differentially expressed genes. Quantitative gene expression analysis (qPCR) and immunohistochemistry was performed on the genes of interest. Statistical analysis for real time PCR was performed on SPSS16 to determine the normalised expression of gene of interest on ocular surface regions.
2010-03-24 | GSE19035 | GEO
Project description:Background: Dupilumab is an IL-4 receptor a mAb inhibiting signaling of IL-4 and IL-13, key drivers of type 2-driven inflammation, as demonstrated by its efficacy in patients with atopic/allergic diseases. Objective: This placebo-controlled, double-blind trial (NCT01979016) evaluated the efficacy, safety, and effects of dupilumab on molecular/cellular lesional and nonlesional skin phenotypes and systemic type 2 biomarkers of patients with moderate-to-severe atopic dermatitis (AD). Methods: Skin biopsy specimens and blood were evaluated from 54 patients randomized 1:1 to weekly subcutaneous doses of 200 mg of dupilumab or placebo for 16 weeks. Results: Dupilumab (vs placebo) significantly improved clinical signs and symptoms of AD, was well tolerated, and progressively shifted the lesional transcriptome toward a nonlesional phenotype (weeks 4-16). Mean improvements in a meta-analysis-derived AD transcriptome (genes differentially expressed between lesional and nonlesional skin) were 68.8% and 110.8% with dupilumab and 210.5% and 55.0% with placebo (weeks 4 and 16, respectively; P < .001). Dupilumab significantly reduced expression of genes involved in type 2 inflammation (IL13, IL31, CCL17, CCL18, and CCL26), epidermal hyperplasia (keratin 16 [K16] and MKi67), T cells, dendritic cells (ICOS, CD11c, and CTLA4), and Th17/Th22 activity (IL17A, IL-22, and S100As) and concurrently increased expression of epidermal differentiation, barrier, and lipid metabolism genes (filaggrin [FLG], loricrin [LOR], claudins, and ELOVL3). Dupilumab reduced lesional epidermal thickness versus placebo (week 4, P 5 .001; week 16, P 5 .0002). Improvements in clinical and histologic measures correlated significantly with modulation of gene expression. Dupilumab also significantly suppressed type 2 serum biomarkers, including CCL17, CCL18, periostin, and total and allergen- specific IgEs. Conclusion: Dupilumab-mediated inhibition of IL-4/IL-13 signaling through IL-4 receptor a blockade significantly and progressively improved disease activity, suppressed cellular/ molecular cutaneous markers of inflammation and systemic measures of type 2 inflammation, and reversed AD-associated epidermal abnormalities. (J Allergy Clin Immunol 2019;143:155-72.)
2019-05-02 | GSE130588 | GEO
Project description:We performed single-cell RNA sequencing of PBMCs from Kimura disease patient succesfully treated with dupilumab to explore the mechanism of action of dupilumab treatment.
2023-06-01 | GSE224144 | GEO
Project description:Mass spectrometry-based proteomics by bottom-up approaches enables the unbiased and sensitive profiling of cellular proteomes and extracellular environments. Recent technological and bioinformatic advances permit identifying of dual biological systems in a single experiment, supporting investigation of infection from the perspective of both a host and pathogen. At the ocular surface, P. aeruginosa are commonly associated with biofilm formation and inflammation of the ocular tissues, causing damage to the eye. The interaction between P. aeruginosa and the immune system at the site of infection describes limitations in clearance of infection and enhanced pathogenesis. Here, we profile the extracellular environment (eye wash) of murine ocular surfaces infected with a clinical isolate of P. aeruginosa and detect neutrophil marker proteins, indicating neutrophil recruitment to the site of infection. In addition, we define the deepest murine corneal proteome to date and detect proteins, categories, and networks critical to the host response to infection. Moreover, we provide the first identification of bacterial-specific proteins in response to the host during bacterial biofilm formation of the eye. We validate our findings through in silico comparisons and enzymatic profiling. Overall, our work provides comprehensive profiling of the host-pathogen interface and uncovers differences between general and site-specific host responses to infection.
2020-01-09 | PXD015362 | Pride
Project description:Itaconate as an adjunct therapy to treat ocular bacterial infection
| PRJNA714613 | ENA
Project description:We report 10 cases of conjunctivitis in atopic dermatitis (AD) patients treated with dupilumab from November 2017 to November 2018 in our institution, who were referred to the ophthalmology department for diagnosis and management of conjunctivitis. We also describe ocular surface findings in these patients before the first injection of dupilumab. During the first 6 months post initiation of dupilumab, incidence of conjunctivitis was 27% (5/18) in patients treated from November 2017 to April 2018 who had not had ocular examination previously. This rate dropped to 12% (3/25) after systematic ophthalmological referral before initiation of dupilumab. Patients who developed conjunctivitis had mean SCORAD score (Scoring Atopic Dermatitis) of 60.4 ± 20 (35-88) and mean EASI score (Eczema Area and Severity Index) of 37 ± 17 (14.6-56). Mean age was 36 years (20-51). Most patients had a long history of AD (> 10 years). Mean delay of ocular surface inflammation was 3.5 months, ranging from 1 to 8 months. One patient had to discontinue dupilumab because of severe follicular conjunctivitis. We observed two clinical patterns of ocular surface diseases: a mild non-specific conjunctivitis with dry eyes, which improved with warm compresses and artificial tears without any recurrence; and a severe dupilumab-induced follicular conjunctivitis without keratitis, which required specific ophthalmological management.
| S-EPMC6692787 | biostudies-literature