Plasma circPTPN22 and its potential target microRNA-200a-3p as novel diagnostic biomarkers in systemic lupus erythematosus patients

T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been found to play important roles in systemic lupus erythematosus (SLE), however, whether Tim-3 is involved in apoptosis of NK cells in SLE remains unknown. The proportion of CD3−CD56+ NK cells and the percentage of AnnexinV+ NK cells were analyzed by flow cytometry in SLE patients and healthy controls. Tim-3 expression on NK cells was also evaluated by flow cytometry. We firstly observed a decreased proportion of NK cells and an increased proportion of apoptotic NK cells in SLE patients. The proportion of apoptotic NK cells was positively correlated with anti-dsDNA and SLEDAI. Tim-3 expression on NK cells was up-regulated in SLE patients. Further analysis showed that Tim-3 expression on NK cells was negatively correlated with the proportion of apoptotic NK cells, anti-dsDNA and SLEDAI, while positively correlated with the proportion of NK cells. The present results suggest that Tim-3 might play roles in SLE by regulating the apoptosis of NK cells and Tim-3 might serve as a potential target for the treatment of SLE.

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Salivary Cytokines as Potential Diagnostic Biomarkers for Systemic Lupus Erythematosus Disease

Mediators of Inflammation ◽

10.1155/2021/8847557 ◽

2021 ◽

Vol 2021 ◽

pp. 1-10

Author(s):

Zeineb Zian ◽

Assia Bouhoudan ◽

Nadira Mourabit ◽

Gholamreza Azizi ◽

Mohcine Bennani Mechita

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Unknown Etiology ◽

Systemic Lupus ◽

Diagnostic Biomarkers ◽

Additional Information ◽

Autoimmune Inflammatory Disease ◽

Cytokine Levels ◽

Variable Clinical Presentation ◽

Significant Attention

Systemic lupus erythematosus (SLE) is a complex autoimmune inflammatory disease characterized by an unknown etiology and a highly variable clinical presentation. This clinical heterogeneity might be explained by dysregulation of tolerance to self and apoptotic mechanisms, overproduction of autoantibodies, and abnormal cytokine levels. Cytokine imbalance levels have been associated with disease activity and severity in SLE patients. In the last years, salivary cytokines related to SLE have gained significant attention and researchers have begun to focus on the identification of cytokines in the saliva of SLE patients using it as a diagnostic fluid for the inflammatory process underlying SLE. This review highlights and summarizes recent studies revealing the cytokines that have been identified in the saliva of individuals with SLE. Data reported and discussed in this report may provide useful additional information to better understand the mechanisms associated with the disease.

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IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2015-208410 ◽

2016 ◽

Vol 75 (11) ◽

pp. 1998-2006 ◽

Cited By ~ 79

Author(s):

Ming Zhao ◽

Yin Zhou ◽

Bochen Zhu ◽

Mengjie Wan ◽

Tingting Jiang ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Promoter Methylation ◽

Lupus Erythematosus ◽

Methylation Level ◽

Renal Damage ◽

Gene Methylation ◽

Systemic Lupus ◽

Diagnostic Biomarkers ◽

Methylation Marker ◽

Highly Sensitive

ObjectiveSystemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker.MethodsIFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren's syndrome (pSS) were used for validation.ResultsSignificant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage.ConclusionsThe methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE.

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The S100 proteins expression in newly diagnosed systemic lupus erythematosus patients: Can they be potential diagnostic biomarkers?

Gene Reports ◽

10.1016/j.genrep.2020.100773 ◽

2020 ◽

Vol 20 ◽

pp. 100773

Author(s):

Mitra Abbasifard ◽

Zahra Kamiab ◽

Mooness Noori ◽

Hossein Khorramdelazad

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

S100 Proteins ◽

Newly Diagnosed ◽

Systemic Lupus ◽

Diagnostic Biomarkers

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A Novel Long Noncoding RNA lincRNA00892 Activates CD4+ T Cells in Systemic Lupus Erythematosus by Regulating CD40L

Frontiers in Pharmacology ◽

10.3389/fphar.2021.733902 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiao Liu ◽

Jinran Lin ◽

Hao Wu ◽

Yilun Wang ◽

Lin Xie ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Flow Cytometry ◽

T Cells ◽

T Cell ◽

Lupus Erythematosus ◽

Healthy Controls ◽

Systemic Lupus ◽

Hnrnp K ◽

Qrt Pcr ◽

Potential Target

Objective: The mechanism of CD4+ T-cell dysfunction in systemic lupus erythematosus (SLE) has not been fully understood. Increasing evidence show that long noncoding RNAs (lncRNAs) can regulate immune responses and take part in some autoimmune diseases, while little is known about the lncRNA expression and function in CD4+ T of SLE. Here, we aimed to detect the expression profile of lncRNAs in lupus CD4+ T cells and explore the mechanism that how lincRNA00892 in CD4+ T cells is involved in the pathogenesis of SLE.Methods: The expression profiles of lncRNAs and mRNAs in CD4+ T cells from SLE patients and healthy controls were detected by microarray. LincRNA00892 and CD40L were chosen for validation by quantitative real-time PCR (qRT-PCR). Coexpression network was conducted to predict the potential target genes of lincRNA00892. Then lincRNA00892 was overexpressed in normal CD4+ T cells via lentivirus transfection. The expression of lincRNA00892 was detected by qRT-PCR. The expression of CD40L was detected by qRT-PCR, western blotting, and flow cytometry, respectively. The expression of CD69 and CD23 was measured by flow cytometry. The secretion of IgG was determined by enzyme-linked immunosorbent assay (ELISA). The proteins targeted by lincRNA00892 were measured by RNA pulldown and subsequent mass spectrometry (MS). The interaction between heterogeneous nuclear ribonucleoprotein K (hnRNP K) and lincRNA00892 or CD40L was detected by RNA immunoprecipitation (RIP) assay.Results: A total of 1887 lncRNAs and 3375 mRNAs were found to be aberrantly expressed in CD4+ T cells of SLE patients compared to healthy controls. LincRNA00892 and CD40L were confirmed to be upregulated in CD4+ T cells of SLE patients by qRT-PCR. The lncRNA–mRNA coexpression network analysis indicated that CD40L was a potential target of lincRNA00892. Overexpression of lincRNA00892 enhanced CD40L protein levels while exerting little influence on CD40L mRNA levels in CD4+ T cells. In addition, lincRNA00892 could induce the activation of CD4+ T cells. Furthermore, lincRNA00892 led to the activation of B cells and subsequent secretion of IgG in a CD4+ T-cell–dependent manner. Finally, hnRNP K was found to be among the proteins pulled down by lincRNA00892, and hnRNP K could bind to lincRNA00892 or CD40L directly.Conclusion: Our results showed that the lncRNA expression profile was altered in CD4+ T cells of SLE. LincRNA00892 possibly contributed to the pathogenesis of SLE by targeting hnRNP K and subsequently upregulating CD40L expression to activate CD4+ T and B cells. These provided us a potential target for further mechanistic studies of SLE pathogenesis.

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Organized Intraglomerular Deposits in NZB Mouse Disease

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100066772 ◽

1971 ◽

Vol 29 ◽

pp. 544-545

Author(s):

Francis R. Comerford ◽

Alan S. Cohen

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Antinuclear Antibodies ◽

Human Systemic Lupus Erythematosus ◽

Systemic Lupus ◽

Glomerular Lesion ◽

Ultrastructural Studies ◽

Dense Deposits ◽

Experimental Nephritis ◽

Glomerular Lesions

Mice of the inbred NZB strain develop a spontaneous disease characterized by autoimmune hemolytic anemia, positive lupus erythematosus cell tests and antinuclear antibodies and nephritis. This disease is analogous to human systemic lupus erythematosus. In ultrastructural studies of the glomerular lesion in NZB mice, intraglomerular dense deposits in mesangial, subepithelial and subendothelial locations were described. In common with the findings in many examples of human and experimental nephritis, including many cases of human lupus nephritis, these deposits were amorphous or slightly granular in appearance with no definable substructure.We have recently observed structured deposits in the glomeruli of NZB mice. They were uncommon and were found in older animals with severe glomerular lesions by morphologic criteria. They were seen most commonly as extracellular elements in subendothelial and mesangial regions. The deposits ranged up to 3 microns in greatest dimension and were often adjacent to deposits of lipid-like round particles of 30 to 250 millimicrons in diameter and with amorphous dense deposits.

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