Systemic lupus erythematosus biomarkers: the challenging quest

Arriens, Cristina; Wren, Jonathan D.; Munroe, Melissa E.; Mohan, Chandra

doi:10.1093/rheumatology/kew407

Cited by 60 publications

(63 citation statements)

References 161 publications

(131 reference statements)

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“…We observed reduced concentrations of TNF, IFN-γ, CCL2, RANTES/CCL5, IL-10, IL-12, IL-12p40, and MIP-1β/CCL4 in the plasma of the DZNep-treated groups compared to controls. All of these cytokines and chemokines have been reported to be elevated in lupus patients (17)(18)(19)(20)(21). Chemokines such as RANTES/CCL5, MCP-1/CCL2, and MIP-1β/CCL4 contribute to lupus pathogenesis by recruiting leukocytes and other effector cells to inflamed tissues, causing damage (17)(18)(19).…”

Section: Cells the Reduction In Cd4-cd8-t Cells (Dn T Cells) Is Of Pmentioning

confidence: 99%

Inhibition of EZH2 ameliorates lupus-like disease inMRL/lprmice

Rohraff

Farkash

et al. 2018

Preprint

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Objective. We previously identified a role for EZH2, a transcriptional regulator in inducing proinflammatory epigenetic changes in lupus CD4+ T cells. This study was undertaken to investigate whether inhibiting EZH2 ameliorates lupus-like disease in MRL/lpr mice.Methods. EZH2 expression levels in multiple cell types in lupus patients were evaluated using flow cytometry and messenger RNA expression data. Inhibition of EZH2 in MRL/lpr mice was achieved by intraperitoneal 3′-deazaneplanocin (DZNep) administration using a preventative and a therapeutic treatment model. Effects of DZNep on animal survival, anti-double-stranded DNA (anti-dsDNA) antibody production, proteinuria, renal histopathology, cytokine production, and T and B cell numbers and percentages were assessed.Results. EZH2 expression levels were increased in whole blood, neutrophils, monocytes, B cells, and CD4+ T cells in lupus patients. In MRL/lpr mice, inhibition of EZH2 by DZNep was confirmed by significant reduction of EZH2 and H3K27me3 in splenocytes. Inhibiting EZH2 with DZNep treatment before or after disease onset improved survival and significantly reduced anti-dsDNA antibody production. DZNep-treated mice displayed a significant reduction in renal involvement, splenomegaly, and lymphadenopathy. Lymphoproliferation and numbers of double-negative T cells were significantly reduced in DZNep-treated mice. Concentrations of circulating cytokines and chemokines, including tumor necrosis factor, interferonγ, CCL2, RANTES/CCL5, interleukin-10 (IL-10), keratinocyte-derived chemokine/ CXCL1, IL-12, IL-12p40, and CCL4/macrophage inflammatory protein 1β, were decreased in DZNep-treated mice.Conclusion. EZH2 is up-regulated in multiple cell types in lupus patients. Therapeutic inhibition of EZH2 abrogates lupus-like disease in MRL/lpr mice, suggesting that EZH2 inhibitors may be repurposed as a novel therapeutic option for lupus patients.

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Section: Cells the Reduction In Cd4-cd8-t Cells (Dn T Cells) Is Of Pmentioning

confidence: 99%

Inhibition of EZH2 ameliorates lupus-like disease inMRL/lprmice

Rohraff

Farkash

et al. 2018

Preprint

View full text Add to dashboard Cite

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“…Others will serve multiple purposes. Specific for this review, a diagnostic biomarker refers to one which will confirm the presence or subtype of a disease, whereas a prognostic biomarker will identify a specific disease manifestation, individuals at risk for development of such disease, or those likely to experience a flare [11]. …”

Section: The Role Of Biomarkers In Sle Diagnosis and Prognosismentioning

confidence: 99%

“…As early as the 1980s IFNα was found elevated in the serum of patients with SLE and positively correlated with clinical disease activity [45–47]. However, due to localized expression and uptake, IFN levels in plasma or serum are transient and therefore difficult to measure [11]. As such, with the advent of microarray and more recently with the use of next-generation RNA sequencing, evaluating gene expression instead has provided a more precise reflection of IFN activity in lupus.…”

Section: Novel Sle Testingmentioning

confidence: 99%

Diagnostic and prognostic tests in systemic lupus erythematosus

Wahezi

Putterman

2017

Best Practice & Research Clinical Rheumatology

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Systemic lupus erythematous (SLE) is a chronic autoimmune inflammatory disease characterized by autoantibodies directed against numerous self-nuclear antigens. Due to the heterogeneous nature of lupus, it has been challenging to identify markers that are sensitive and specific enough for its diagnosis and monitoring. However, with the sequencing of the human genome, rapid development of high throughput approaches has allowed for a better understanding of the etiopathogenesis of complex diseases, including SLE. Here we will present a review of the latest advancements in biomarker discovery during the ‘omics’ era, using these novel technologies, for assisting in the diagnosis and prognosis of patients with SLE.

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“…Elevated IFN-γ levels were detected in the MRL-Fas lpr lupus mice especially at the late stage of disease [24][25][26][27][28][29]. Transgenic mice with over-expressed IFN-γ would develop T-cell dependent lupus-like syndrome and deposits of antinuclear autoantibodies in kidney [6,30]. Jacob et al firstly came up with the idea that IFN-γ played an important role in the pathogenesis of lupus [31].…”

Section: Ifn-γ and Its Regulatory Roles In Slementioning

confidence: 99%

“…With the advance of cell signaling profile in SLE, a series of non-traditional and emerging biomarkers including cytokines, growth factors, chemokines and acute phase reactants were found to have potential clinical effects in SLE. Diverse characteristics and introduction of traditional and non-traditional biomarkers for SLE were described elsewhere [6]. Cross communications among various cells, especially immune cells, play vital roles in the pathogenesis of SLE and cytokines gain much attention for their abilities to mediate adjacent and long-distance communications among immune cells.…”

Section: Introductionmentioning

confidence: 99%

Biological Features of IL-12 and IFN-? in the Pathogenesis of Systematic Lupus Erythematosus

Lu¹,

Wang²,

Wang³

et al. 2017

J Clin Exp Pathol

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Systemic lupus erythmatosus is a chronic autoimmune disease characterized by abnormal immune response with overproduction of auto-antibodies, self-destructive complexes and hyperactivity of both T and B lymphocytes. Although the exact pathogenesis of SLE remains unclear, it has been found that the imbalance of Th1/Th2, subsequent cytokines and anti-or pro-inflammatory mediators could reflect the stage and phenotype of SLE. Among diverse cytokines involved in the disease progression, IL-12 and IFN-γ gain much attention for their biological functions in SLE. There existed many divergences on the expression level of IL-12 while few conflicts were demonstrated on elevated level of IFN-γ in SLE patients. By analysis of gene polymorphisms, it was suggested that positive correlations were observed between IL-12B rs3212227, IL-12B rs17860508 and susceptibility to and severity of SLE in Polish patients. In addition, the combination of the IL-12B rs17860508 GC allele and/or IL-12B rs3212227 C allele could increase the risk of SLE progression and/or severity of SLE parameters in Polish population. Furthermore, it was also found that the incorporation of IFN-γ R 1 Met 14/Val 14 and IFN-γ R 2 Gln 64/Gln 64 genotypes was a potential risk factor for SLE. Based on the previous researches, IL-12 and IFN-γ targeted gene therapy was developed and found to be effective in murine lupus. Intramuscular injection of IFN-γR/IgG1Fc fusion protein encoded cDNA and suppressive ODN was found to decrease the severity of disease and promote survival of lupus mice. On the other hand, intramuscular injection of IL-12 and IL-18 encoded plasmids alone or together was also observed to have therapeutic effects on murine lupus. All in all, this review mainly introduces the biological features and the potential therapeutic effects of IL-12 and IFN-γ in the pathogenesis of SLE.

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Systemic lupus erythematosus biomarkers: the challenging quest

Cited by 60 publications

References 161 publications

Inhibition of EZH2 ameliorates lupus-like disease inMRL/lprmice

Inhibition of EZH2 ameliorates lupus-like disease inMRL/lprmice

Diagnostic and prognostic tests in systemic lupus erythematosus

Biological Features of IL-12 and IFN-? in the Pathogenesis of Systematic Lupus Erythematosus

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