Type I IFN signature in childhood-onset systemic lupus erythematosus: a conspiracy of DNA- and RNA-sensing receptors?

Wahadat, M. Javad; Bodewes, Iris L A; Maria, Naomi I.; Helden-Meeuwsen, Cornelia G van; Dijk-Hummelman, Annette van; Steenwijk, Eline C.; Kamphuis, Sylvia; Versnel, Marjan A.

doi:10.1186/s13075-017-1501-z

Cited by 51 publications

(44 citation statements)

References 32 publications

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“…Positive blood type-1 IFN gene signatures also occur in substantial numbers of patients with systemic autoimmune disease, including pSS, SLE or SSc. [28][29][30][31] We did not observe a correlation between the disease-specific type-1 IFN gene signature score and serum C1q level in systemic autoimmune disease (pSS, SLE or SLE). Several studies did identify transcriptional differences, as well as similarities, in type-1 IFN-inducible gene signatures between various autoimmune diseases, TB, and normal immune responses, supporting the use of disease-specific IFN gene signatures.…”

Section: Discussioncontrasting

confidence: 60%

“…Substantial subsets of patients with pSS, SLE and SSc also display a positive type-1 IFN signature. [28][29][30][31] represents a more general phenomenon, we also determined the relation between serum C1q levels and peripheral blood type-1 IFN signature scores in pSS, SLE and SSc patients. Serum C1q did not show any correlation with the peripheral blood type-1 IFN signature scores in any of these systemic autoimmune diseases (Supplementary figure 1).…”

Section: Inverse Correlation Between Serum C1q Levels and Peripheral mentioning

confidence: 99%

“…Sera from three previously collected cohorts, two TB cohorts from Indonesia (from now on designated as cohort 1 47 and 2 48 ) and one cohort consisting of systemic autoimmune patients from mainly Caucasian origin (from now on designated as cohort 3 [28][29][30] ), were included in this study. All individuals from cohorts 1 and 3 and all TB patients from cohort 2 were HIV negative, and healthy controls from cohort 2 were largely untested.…”

Section: Patients and Controlsmentioning

confidence: 99%

“…22 In addition, from cohort 3, the systemic autoimmune disease-related peripheral blood type-1 IFN signature scores were available and determined as previously described. [28][29][30] Genes comprising the diseaserelated type-1 IFN signatures, as well as the formula used to calculate the type-1 IFN signature score, are provided in Supplementary table 1.…”

Section: Peripheral Blood Type-1 Ifn Gene Signaturesmentioning

confidence: 99%

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Inverse correlation between serum complement component C1q levels and whole blood type‐1 interferon signature in active tuberculosis and QuantiFERON‐positive uveitis: implications for diagnosis

et al. 2020

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Objectives. To examine the relation between serum C1q levels and blood type-1 interferon signature (type-1 IFN signature) in active pulmonary tuberculosis (APTB) and to determine whether combined measurement of serum C1q and type-1 IFN signature may add to the diagnosis of QuantiFERON-positive (QFT +) patients with uveitis of unknown cause. Methods. C1q was determined (ELISA) in serum from two distinct Indonesian cohorts, and in total, APTB (n = 72), QFT + uveitis of unknown aetiology (n = 58), QFT À uveitis (n = 51) patients and healthy controls (HC; n = 73) were included. The type-1 IFN signature scores were previously determined. Results. Serum C1q was higher in APTB than HC (P < 0.001). APTB patients with uveitis had higher serum C1q than APTB patients without uveitis (P = 0.0207). Serum C1q correlated inversely with type-1 IFN signature scores in APTB (P = 0.0036, r 2 = 0.3526), revealing that these biomarkers for active TB disease can be mutually exclusive. Stratification of QFT + patients with uveitis of unknown cause, by serum C1q and type-1 IFN signature, yielded four groups with different likelihood of suffering from active TB uveitis. Conclusion. Serum C1q is elevated in APTB, especially in those cases with uveitis. We propose that combined measurement of blood type-1 IFN signature and serum C1q may provide added value in the diagnosis of active TB disease. Combined measurement of type-1 IFN signature and serum C1q in QFT + patients without signs of active TB disease, but suffering from uveitis of unknown cause, may be of help to identify cases

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Section: Discussioncontrasting

confidence: 60%

Section: Inverse Correlation Between Serum C1q Levels and Peripheral mentioning

confidence: 99%

Section: Patients and Controlsmentioning

confidence: 99%

Section: Peripheral Blood Type-1 Ifn Gene Signaturesmentioning

confidence: 99%

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Inverse correlation between serum complement component C1q levels and whole blood type‐1 interferon signature in active tuberculosis and QuantiFERON‐positive uveitis: implications for diagnosis

et al. 2020

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“…[ 59 ] DDX58 gene plays an important role in activating NF-κ B pathway and plays an important role in the pathogenesis of dermatomyositis. [ 60 ] It has been found that DDX58 gene is significantly up regulated in psoriasis patients and psoriasis like mice. [ 61 ]…”

Section: Discussionmentioning

confidence: 99%

Study on the differentially expressed genes and signaling pathways in dermatomyositis using integrated bioinformatics method

Liu

Zhao

2020

Medicine

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Dermatomyositis is a common connective tissue disease. The occurrence and development of dermatomyositis is a result of multiple factors, but its exact pathogenesis has not been fully elucidated. Here, we used biological information method to explore and predict the major disease related genes of dermatomyositis and to find the underlying pathogenic molecular mechanism. The gene expression data of GDS1956, GDS2153, GDS2855, and GDS3417 including 94 specimens, 66 cases of dermatomyositis specimens and 28 cases of normal specimens, were obtained from the Gene Expression Omnibus database. The 4 microarray gene data groups were combined to get differentially expressed genes (DEGs). The gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments of DEGs were operated by the database for annotation, visualization and integrated discovery and KEGG orthology based annotation system databases, separately. The protein–protein interaction networks of the DEGs were built from the STRING website. A total of 4097 DEGs were extracted from the 4 Gene Expression Omnibus datasets, of which 2213 genes were upregulated, and 1884 genes were downregulated. Gene ontology analysis indicated that the biological functions of DEGs focused primarily on response to virus, type I interferon signaling pathway and negative regulation of viral genome replication. The main cellular components include extracellular space, cytoplasm, and blood microparticle. The molecular functions include protein binding, double-stranded RNA binding and MHC class I protein binding. KEGG pathway analysis showed that these DEGs were mainly involved in the toll-like receptor signaling pathway, cytosolic DNA-sensing pathway, RIG-I-like receptor signaling pathway, complement and coagulation cascades, arginine and proline metabolism, phagosome signaling pathway. The following 13 closely related genes, XAF1, NT5E, UGCG, GBP2, TLR3, DDX58, STAT1, GBP1, PLSCR1, OAS3, SP100, IGK, and RSAD2, were key nodes from the protein–protein interaction network. This research suggests that exploring for DEGs and pathways in dermatomyositis using integrated bioinformatics methods could help us realize the molecular mechanism underlying the development of dermatomyositis, be of actual implication for the early detection and prophylaxis of dermatomyositis and afford reliable goals for the curing of dermatomyositis.

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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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Type I IFN signature in childhood-onset systemic lupus erythematosus: a conspiracy of DNA- and RNA-sensing receptors?

Cited by 51 publications

References 32 publications

Inverse correlation between serum complement component C1q levels and whole blood type‐1 interferon signature in active tuberculosis and QuantiFERON‐positive uveitis: implications for diagnosis

Inverse correlation between serum complement component C1q levels and whole blood type‐1 interferon signature in active tuberculosis and QuantiFERON‐positive uveitis: implications for diagnosis

Study on the differentially expressed genes and signaling pathways in dermatomyositis using integrated bioinformatics method

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

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