Dermatomyositis flare on imiquimod therapy highlights a crucial role of aberrant TLR7 signalling

Meyer, Alain; Alsaleh, Ghada; Heuschling, Claude; Gottenberg, Jacques-Éric; Georgel, Philippe; Geny, Benard; Bahram, Seiamak; Sibilia, Jean

doi:10.1136/rmdopen-2016-000294

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…Previous study confirmed that CX3CR1 [723], S100A12 [724], CD177 [725], PF4 [726], MPO (myeloperoxidase) [727], CD5L [728], F11 [729], S100A8 [730], PGLYRP1 [731], GPR15 [732], BPI (bactericidal permeability increasing protein) [733], AQP4 [734], BDNF (brain derived neurotrophic factor) [735], CXCL10 [736], FCGR3B [737], S100A9 [738], IL1B [739], CXCR1 [740], CXCR2 [741], AFF3 [742], WNT3A [743], FCN3 [744], AZGP1 [745], CD36 [746], PCSK9 [747], GPX3 [748], FGF2 [749], SHH (sonic hedgehog signaling molecule) [750], SLC7A11 [751], VIP (vasoactive intestinal peptide) [752], KL (klotho) [753], APOA1 [754], RASGRF1 [755], CD244 [756], TLR3 [757], NLRP12 [758], SNX10 [759], TLR8 [760], GATA3 [761], CCR2 [762], TLR7 [763], CCRL2 [764], EFNB2 [765], FZD8 [766], CAV1 [767], CR1 [768], MEFV (MEFV innate immuity regulator, pyrin) [769], SUCNR1 [770], GCA (grancalcin) [771] and FOXJ1 [663] are strongly associated with rheumatoid arthritis. S100A12 [772], MPO (myeloperoxidase) [773], S100A8 [774], CXCL10 [775], S100A9 [774], CD244 [775] and TLR7 [777] have been linked to dermatomyositis. MPO (myeloperoxidase) [778] have been proposed as novel biomarkers for mixed connective tissue disease progression.…”

Section: Discussionmentioning

confidence: 99%

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis and key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the pathogenesis of IPF and related key genes, so as to investigate the potential molecular pathogenesis of IPF and provide guidance for clinical treatment. Next generation sequencing dataset GSE213001 was obtained from Gene Expression Omnibus (GEO), the differentially expressed genes (DEGs) were identified between IPF and normal control group. The DEGs between IPF and normal control group were screened with the DESeq2 package of R language. The Gene Ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed. Using the g:Profiler, the function and pathway enrichment analysis of DEGs were performed. Then, a protein protein interaction (PPI) network was constructed via the Integrated Interactions Database (IID) database. Cytoscape with Network Analyzer was used to identify the hub genes. miRNet and NetworkAnalyst database was used to construct the targeted microRNAs (miRNAs) and transcription factors (TFs) of the hub genes. Finally receiver operating characteristic (ROC) curve analysis was used to validates the hub genes. A total of 958 DEGs were screened out in this study, including 479 up regulated genes and 479 down regulated genes. Most of the DEGs were significantly enriched in response to stimulus, GPCR ligand binding, microtubule-based process and defective GALNT3 causes HFTC. In combination with the results of the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, hub genes including LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8 and EFHC2 were selected. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of IPF, and provide a novel strategy for clinical therapy.

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Section: Discussionmentioning

confidence: 99%

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2023

Preprint

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“…This may explain why several groups have reported new diagnoses of SLE or severe SLE flares after COVID-19 vaccinations as we have described for DM ( 30 – 33 ). As TLR7 plays a prominent role in the pathogenesis of DM ( 34 ), we suspect that TLR7 agonists such as those present in RNA/DNA vaccines utilized for COVID-19 may be sufficient to promote inflammatory signals associated with DM. Another possibility may include a role for vaccine encoded spike proteins promoting a “superantigen” response, which promotes systemic immune dysregulatory responses in genetically predisposed individuals, as previously suggested ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

A case series of dermatomyositis following SARS-CoV-2 vaccination

et al. 2022

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Background/ObjectiveThe most significant adverse events following SARS-CoV-2 vaccination are myocarditis and pericarditis. Myositis and dermatomyositis have been reported following SARS-CoV-2 infection, but vaccine-induced dermatomyositis (DM) has not been reported. Our case series aimed to characterize new onset dermatomyositis or disease-related flares following SARS-CoV-2 vaccination.Materials and methodsA total of 53 patients from our institution with a new or pre-existing diagnosis of DM were recruited and consented. Phone interviews were conducted to obtain vaccination status and symptoms following vaccination. Electronic medical records were reviewed to extract age, sex, autoantibody profiles, comorbidities, immunomodulatory therapies, creatine kinase (CK) values, and SARS-CoV-2 vaccination dates from the provincial vaccination registry. For patients who reported disease flares, records were reviewed for the onset and nature of symptoms, extent of organ involvement and changes in immunomodulation.ResultsOn average, patients received 2.62 vaccine doses (range 1–3 doses). A total of 3 of 51 patients (5.88%) experienced dermatomyositis symptoms following vaccination. Two patients were newly diagnosed with dermatomyositis, one requiring hospitalization. Reported symptom onset following vaccination ranged from 1 to 30 days. Of note, all of these patients had normal CK values, even though there was muscle biopsy-confirmed myositis in one patient. Eight patients in the cohort (15.1%) had asymptomatic CK elevation (<1.5 X ULN).ConclusionNew onset dermatomyositis or flare up of pre-existing dermatomyositis may be a rare complication in SARS-CoV-2 vaccination although no studies can support a true correlation. Several pathophysiologic mechanisms are proposed.

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Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis

Giriyappagoudar,

Vastrad,

Horakeri

et al. 2023

Biomedicines

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Idiopathic pulmonary fibrosis (IPF) is a chronic progressive lung disease with reduced quality of life and earlier mortality, but its pathogenesis and key genes are still unclear. In this investigation, bioinformatics was used to deeply analyze the pathogenesis of IPF and related key genes, so as to investigate the potential molecular pathogenesis of IPF and provide guidance for clinical treatment. Next-generation sequencing dataset GSE213001 was obtained from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified between IPF and normal control group. The DEGs between IPF and normal control group were screened with the DESeq2 package of R language. The Gene Ontology (GO) and REACTOME pathway enrichment analyses of the DEGs were performed. Using the g:Profiler, the function and pathway enrichment analyses of DEGs were performed. Then, a protein–protein interaction (PPI) network was constructed via the Integrated Interactions Database (IID) database. Cytoscape with Network Analyzer was used to identify the hub genes. miRNet and NetworkAnalyst databaseswereused to construct the targeted microRNAs (miRNAs), transcription factors (TFs), and small drug molecules. Finally, receiver operating characteristic (ROC) curve analysis was used to validate the hub genes. A total of 958 DEGs were screened out in this study, including 479 up regulated genes and 479 down regulated genes. Most of the DEGs were significantly enriched in response to stimulus, GPCR ligand binding, microtubule-based process, and defective GALNT3 causes HFTC. In combination with the results of the PPI network, miRNA-hub gene regulatory network and TF-hub gene regulatory network, hub genes including LRRK2, BMI1, EBP, MNDA, KBTBD7, KRT15, OTX1, TEKT4, SPAG8, and EFHC2 were selected. Cyclothiazide and rotigotinethe are predicted small drug molecules for IPF treatment. Our findings will contribute to identification of potential biomarkers and novel strategies for the treatment of IPF, and provide a novel strategy for clinical therapy.

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Dermatomyositis flare on imiquimod therapy highlights a crucial role of aberrant TLR7 signalling

Cited by 3 publications

References 11 publications

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

Study on potential differentially expressed genes in idiopathic pulmonary fibrosis by bioinformatics and next generation sequencing data analysis

A case series of dermatomyositis following SARS-CoV-2 vaccination

Study on Potential Differentially Expressed Genes in Idiopathic Pulmonary Fibrosis by Bioinformatics and Next-Generation Sequencing Data Analysis

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