<scp>IRF</scp>7 gene expression profile and methylation of its promoter region in patients with systemic sclerosis

Rezaei, Ramazan; Mahmoudi, Mahdi; Gharibdoost, Farhad; Kavosi, Hoda; Dashti, Navid; Imeni, Vahideh; Jamshidi, Ahmadreza; Aslani, Saeed; Mostafaei, Shayan; Vodjgani, Mohammad

doi:10.1111/1756-185x.13175

Cited by 26 publications

(26 citation statements)

References 52 publications

(93 reference statements)

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“…In addition, a female sample with no family history of autoimmune diseases has been reported to develop SSc after IFN-a therapy, implicating the strong correlation between type I IFN and SSc (Solans et al, 2004). Further, multiple type I IFNÀassociated genes were found to be in association with the pathogenesis of SSc from genetic association studies, including STAT4, IFR5, IRF7, and IRF8 (Arismendi et al, 2015;Rezaei et al, 2017;Wang J et al, 2014;Xu et al, 2016;Yi et al, 2013). In summary, dysfunctional type I IFNÀassociated pathway involves in the pathogenesis, fibrosis and disease severity, and progression of SSc.…”

Section: Discussionmentioning

confidence: 91%

Genome-Wide DNA Methylation Analysis in Systemic Sclerosis Reveals Hypomethylation of IFN-Associated Genes in CD4+ and CD8+ T Cells

Ding

Wang

et al. 2018

Journal of Investigative Dermatology

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Epigenetic modifications, including DNA methylation, play an important role in the pathogenesis of autoimmune diseases. In this study, we characterized the DNA methylome in primary T cells of patients with systemic sclerosis. Genome-wide DNA methylation assays of CD4 and CD8 T cells from 24 systemic sclerosis patients and 24 matched controls were conducted and differentially methylated regions were validated. In the discovery stage, we found that hypomethylation of genes involved in the type I IFN signaling pathway was significantly enriched in both CD4 (P = 7.59 × 10) and CD8 (P = 2.10 × 10) differentially methylated regions. In the validation stage, we confirmed these changes for five type I IFN-associated genes. In addition, protein levels of both type I IFN-α (P < 0.0001) and β (P = 0.002) were significantly elevated in the sera of systemic sclerosis patients. Moreover, significant associations between type I IFN-α/β protein levels with the DNA methylation status as well as the expression profiles of these IFN-associated genes were confirmed. In conclusion, the type I IFN pathway is dysfunctional at the epigenetic level in systemic sclerosis patients, indicating that hypomethylation and upregulation of type I IFN-associated genes might be critical in systemic sclerosis pathogenesis.

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Section: Discussionmentioning

confidence: 91%

Genome-Wide DNA Methylation Analysis in Systemic Sclerosis Reveals Hypomethylation of IFN-Associated Genes in CD4+ and CD8+ T Cells

Ding

Wang

et al. 2018

Journal of Investigative Dermatology

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“…Epigenetics is considered as heritable changes of expression of genes, in which nucleotide sequence of DNA does not change. DNA methylation, histone modifications, and microRNA‐related gene expression regulation are regarded as the main mechanisms of epigenetic regulations (Aslani, Mahmoudi, Garshasbi, et al, ; Karami et al, ; Rezaei et al, ). Numerous research have established that several abnormalities in these mechanisms eventuate in to development of autoimmune disease such as RA (Ahmadi et al, 2017; Aslani, Mahmoudi, Karami, et al, ).…”

Section: Epigenetic Therapy In Ramentioning

confidence: 99%

Strategies toward rheumatoid arthritis therapy; the old and the new

Abbasi

Mousavi

Jamalzehi

et al. 2018

Journal Cellular Physiology

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295

181

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Currently, medications used to treat rheumatoid arthritis (RA) are glucocorticoids (GCs) and nonsteroidal anti‐inflammatory drugs (NSAIDs), predominantly used for controlling the pain and inflammation, disease‐modifying antirheumatic drugs (DMARDs), administered as first‐line medication for newly diagnosed RA cases, and biological therapies, used to target and inhibit specific molecules of the immune and inflammatory responses. NSAIDs and other GCs are effective in alleviating the pain, inflammation, and stiffness due to RA. DMARDs that are used for RA therapy are hydroxychloroquine, methotrexate, leflunomide, and sulfasalazine. The biological therapies, on the contrary, are chimeric anti‐CD20 monoclonal antibody, rituximab, inhibitors of tumor necrosis factor‐α (TNF‐α) like etanercept, infliximab, and adalimumab, a recombinant inhibitor of interleukin‐1 (IL‐1), anakinra, and costimulation blocker, abatacept. Moreover, newly under evaluation biological therapies include new TNF‐α inhibitors, JAK inhibitors, anti‐interleukin‐6‐receptor monoclonal antibodies (mABs), and antibodies against vital molecules involved in the survival and development of functional B cells. The new strategies to treat RA has improved the course of the disease and most of the patients are successful in remission of the clinical manifestations if the diagnosis of the disease occur early. The probability of remission increase if the diagnosis happens rapidly and treat‐to‐target approach are implemented. In this review article, we have attempted to go through the treatment strategies for RA therapy both the routine ones and those which have been developed over the past few years and currently under investigation.

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“…IRF7 mRNA expression was significantly upregulated in the bleomycin-induced and tight-skin mouse models as well as in peripheral blood mononuclear cells and dermal fibroblasts from patients ( 100 ). Moreover, patients with different IRF7 SNPs (rs1131665: P = 6.14 × 10 −4 , OR = 0.78; rs4963128: P = 6.14 × 10 −4 , OR = 0.79; rs702966: P = 3.83 × 10 −3 , OR = 0.82; and rs2246614: P = 3.83 × 10 −3 , OR = 0.83) were mostly related to ACA-positivity ( 67 , 100 , 101 ), thus supporting the fact that the IRF7 locus represents a common risk factor for ACA production.…”

Section: Classical Disease-specific Autoantibodies In Clinical Manifementioning

confidence: 99%

Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification

et al. 2020

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Systemic sclerosis (SSc) is an autoimmune disease characterized by abnormalities in microcirculation, extracellular matrix accumulation, and immune activation. Autoantibodies are markers of immune abnormalities and provide diagnostic and predictive value in SSc. Anti-topoisomerase antibodies (ATAs), anticentromere antibodies (ACAs), and anti-RNA polymerase antibodies (ARAs) are the three classical specific antibodies with the highest availability and stability. In this review, we provide an overview of the recent progress in SSc research with respect to ATAs, ACAs, and ARAs, focusing on their application in distinguishing clinical phenotypes, such as malignancy and organ involvement, identifying genetic background in human leukocyte antigen (HLA) or non-HLA alleles, and their potential roles in disease pathogenesis based on the effects of antigen-antibody binding. We finally summarized the novel analysis using ATAs, ACAs, and ARAs on more detailed disease clusters. Considering these advantages, this review emphasizes that classical SSc-specific autoantibodies are still practical and have the potential for patient and risk stratification with applications in precise medicine for SSc.

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IRF7 gene expression profile and methylation of its promoter region in patients with systemic sclerosis

Abstract: It is suggested that hypomethylation of the IRF7 promoter might play a role in SSc pathogenesis, probably through promoting the IRF7 expression in PBMCs of patients with SSc.

Cited by 26 publications

References 52 publications

Genome-Wide DNA Methylation Analysis in Systemic Sclerosis Reveals Hypomethylation of IFN-Associated Genes in CD4+ and CD8+ T Cells

Genome-Wide DNA Methylation Analysis in Systemic Sclerosis Reveals Hypomethylation of IFN-Associated Genes in CD4+ and CD8+ T Cells

Strategies toward rheumatoid arthritis therapy; the old and the new

Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification

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