Interferon-inducible Mx1 protein is highly expressed in renal tissues from treatment-naïve lupus nephritis, but not in those under immunosuppressive treatment

Shimizu, Yasuhiko; Yasuda, Shinsuke; Kimura, Taichi; Nishio, S.; Kono, Michihiro; Ohmura, Koichiro; Shimamura, Sanae; Fujieda, Yuichiro; Kato, Masaaki; Oku, Kenji; Bohgaki, Toshiyuki; Fukasawa, Yuichiro; Tanaka, Shinya; Atsumi, Tatsuya

doi:10.1080/14397595.2017.1404711

Cited by 19 publications

(13 citation statements)

References 51 publications

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“…MX1 is downstream in the type I IFN pathway and is an important component of the early innate immune system, as it plays a role in the IFN-induced antiviral response against various viruses, but its role in response to IFN stimulation in the absence of virus has yet to be determined (39)(40)(41). MX1 hypomethylation, increased RNA expression, and higher protein concentrations are consistently observed in SLE patients (20,(42)(43)(44). Multiple CpGs associated with MX1 were observed to be highly associated with SLE status in this analysis, and methylation at 2 MX1 CpGs revealed almost perfect separation of AA patients with SLE from controls, leading us to hypothesize that a targeted assay for MX1 methylation would be fruitful in diagnosing SLE.…”

Section: Discussionmentioning

confidence: 99%

Population‐Specific Patterns of Epigenetic Defects in the B Cell Lineage in Patients With Systemic Lupus Erythematosus

Breitbach

Ramaker

Roberts

et al. 2019

Arthritis & Rheumatology

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Objective. To determine the stage of B cell development at which a systemic lupus erythematosus (SLE)associated DNA methylation signature originates in African American (AA) and European American (EA) subjects, and to assess whether epigenetic defects in B cell development patterns could be predictive of SLE status in individual and mixed immune cell populations.Methods. B cells from AA patients (n = 31) and EA patients (n = 49) with or without SLE were sorted using fluorescence-activated cell sorting into 5 B cell subsets. DNA methylation, measured at ~460,000 CpG sites, was interrogated in each subset. Enrichment analysis of transcription factor interaction at SLE-associated methylation sites was performed. A random forests algorithm was used to identify an epigenetic signature of SLE in the B cell subsets, which was then validated in an independent cohort of AA and EA patients and healthy controls.Results. Regression analysis across all B cell stages resulted in identification of 60 CpGs that reached genomewide significance for SLE-associated methylation differences (P ≤ 1.07 × 10 −7 ). Interrogation of ethnicity-specific CpGs associated with SLE revealed a hypomethylated pattern that was enriched for interferon (IFN)-regulated genes and binding of EBF1 in AA patients (each P < 0.001). AA patients with SLE could be distinguished from healthy controls when the predictive model developed with the transitional B cell subset was applied to other B cell subsets (mean receiver operating characteristic [ROC] area under the curve [AUC] 0.98), and when applied to CD19+ pan-B cells (mean ROC AUC 0.95) and CD4+ pan-T cells (mean ROC AUC 0.97) from the independent validation cohort.Conclusion. These results indicate that SLE-specific methylation patterns are ethnicity dependent. A pattern of epigenetic changes near IFN-regulated genes early in B cell development is a hallmark of SLE in AA female subjects. EBF1 binding sites are highly enriched for significant methylation changes, implying that this may be a potential regulator of SLE-associated epigenetic changes.

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Section: Discussionmentioning

confidence: 99%

Population‐Specific Patterns of Epigenetic Defects in the B Cell Lineage in Patients With Systemic Lupus Erythematosus

Breitbach

Ramaker

Roberts

et al. 2019

Arthritis & Rheumatology

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“…Kidney biopsies of patients with SLE show increased expression of IFN-inducible genes108–110 and pDCs accumulate in glomeruli of patients with active disease 50. A stronger IFN signature is observed in glomeruli and renal tubule in patients with immunosuppressive naïve SLE with nephritis compared with patients with SLE nephritis having received immunosuppressive treatment 111. In kidney tissue, IFN-β can induce podocyte cell death and increase permeability whereas both IFN-α and IFN-β suppress renal progenitor cell differentiation into mature podocytes,112 resulting in podocyte loss, proteinuria and impaired glomerular repair.…”

Section: Introductionmentioning

confidence: 99%

Interferon pathway in SLE: one key to unlocking the mystery of the disease

2019

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SLE is characterised by an activation of the interferon (IFN) system, which leads to an increased expression of IFN-regulated genes. The reasons behind the IFN signature in SLE are (1) the existence of endogenous IFN inducers, (2) activation of several IFN-producing cell types, (3) production of many different IFNs, (4) a genetic setup promoting IFN production and (5) deficient negative feedback mechanisms. The consequences for the immune system is a continuous stimulation to an immune response, and for the patient a number of different organ manifestations leading to typical symptoms for SLE. In the current review, we will present the existing knowledge of the IFN system and pathway activation in SLE. We will also discuss how this information can contribute to our understanding of both the aetiopathogenesis and some organ manifestations of the disease. We will put forward some issues that are unresolved and should be clarified in order to make a proper stratification of patients with SLE, which seems important when selecting a therapy aiming to downregulate the IFN system.

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“…Another hub gene interferon-induced is MX1. It has been reported that this molecule is highly expressed during renal disease like lupus nephritis, and that this could be possible to cause kidney inflammation [87]. Moreover, another study supports this gene behavior.…”

Section: Interactome Analysis and Hub Genes Identificationmentioning

confidence: 59%

Discovering hub genes involved in the pathophysiological impact of COVID-19 on diabetes kidney disease by differential gene expression and interactome analysis

Osuna-Martínez

Aviña-Padilla

Olimón-Andalón

et al. 2022

Preprint

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Diabetic kidney disease (DKD) is a frequently chronic kidney pathology derived from diabetes comorbidity. This condition has irreversible damage, and its risk factor increases with SARS-CoV-2 infection. The prognostic outcome for diabetic patients with COVID-19 is dismal, even with intensive medical treatment. However, there is still scarce information on critical genes involved in the pathophysiological impact of COVID-19 on DKD. Herein, we characterize differential expression gene (DEG) profiles and determine hub genes undergoing transcriptional reprogramming in both disease conditions. Out of 995 DEGs, we identified 42 DEGs shared with COVID-19 pathways. Enrichment analysis elucidated that they are significantly induced with implications for immune and inflammatory responses. By performing a protein-protein interaction (PPI) network and applying topological methods, we determine the following five hub genes STAT1, IRF7, ISG15, MX1, and OAS1. Then, by network deconvolution, we determine their co-expressed gene modules. Moreover, we validate the conservancy of their upregulation using the Coronascape database (DB). Finally, tissue-specific regulation of the five predictive hub genes indicates that OAS1 and MX1 expression levels are lower in healthy kidney tissue. Altogether, our results suggest that these genes could play an essential role in developing severe outcomes of COVID-19 in DKD patients.

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Interferon-inducible Mx1 protein is highly expressed in renal tissues from treatment-naïve lupus nephritis, but not in those under immunosuppressive treatment

Cited by 19 publications

References 51 publications

Population‐Specific Patterns of Epigenetic Defects in the B Cell Lineage in Patients With Systemic Lupus Erythematosus

Population‐Specific Patterns of Epigenetic Defects in the B Cell Lineage in Patients With Systemic Lupus Erythematosus

Interferon pathway in SLE: one key to unlocking the mystery of the disease

Discovering hub genes involved in the pathophysiological impact of COVID-19 on diabetes kidney disease by differential gene expression and interactome analysis

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