FRI0262 Differences in serum microrna profile in active systemic lupus erythematosus and healthy controls

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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Steroid-Induced Morbidity Mimicking Active Systemic Lupus Erythematosus

Annals of Internal Medicine ◽

10.7326/0003-4819-78-4-558 ◽

1973 ◽

Vol 78 (4) ◽

pp. 558 ◽

Cited By ~ 2

Author(s):

JOE G. HARDIN

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Active Systemic Lupus Erythematosus ◽

Systemic Lupus

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Elevated levels of IL-24 in systemic lupus erythematosus patients

Lupus ◽

10.1177/0961203319845476 ◽

2019 ◽

Vol 28 (6) ◽

pp. 748-754 ◽

Cited By ~ 1

Author(s):

R C Li ◽

J Guo ◽

L C Su ◽

A F Huang

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Inflammatory Cytokine ◽

Activity Index ◽

Clinical Manifestations ◽

Mrna Levels ◽

Healthy Controls ◽

Systemic Lupus ◽

Good Ability

Objective This study aimed to assess IL-24 levels and their association with clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods There were 75 patients with SLE and 58 healthy controls recruited in this study. Serum levels of IL-24 were measured by enzyme-linked immunosorbent assays, and mRNA levels of IL-24 were tested by quantitative real-time polymerase chain reaction . The area under the curve of the receiver operating characteristic (ROC) curve was used for diagnostic ability of the inflammatory cytokine. Results Serum IL-24 levels were significantly higher in SLE patients than that in healthy controls. SLE patients with nephritis had higher IL-24 levels than those without nephritis. Active SLE patients showed higher expression of IL-24 as compared to less active disease patients. The mRNA levels of IL-24 were much higher in SLE patients. Correlation analysis showed significant correlation between serum IL-24 levels and SLE disease activity index. In addition, ROC analysis may suggest good ability of serum IL-24 in differentiating SLE. Conclusion The inflammatory cytokine correlated with SLE disease activity, and may be involved in this disease pathogenesis.

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mRNA expression analysis confirms CD44 splicing impairment in systemic lupus erythematosus patients

Lupus ◽

10.1177/09612033211004725 ◽

2021 ◽

pp. 096120332110047

Author(s):

Andrea Latini ◽

Lucia Novelli ◽

Fulvia Ceccarelli ◽

Cristiana Barbati ◽

Carlo Perricone ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

Mrna Expression ◽

Lupus Erythematosus ◽

Mononuclear Cells ◽

Direct Sequencing ◽

Healthy Controls ◽

Systemic Lupus ◽

Peripheral Tissues ◽

Variant Isoforms

Background Systemic Lupus Erythematosus (SLE) is a complex chronic autoimmune disease characterized by several immunological alterations. T cells have a peculiar role in SLE pathogenesis, moving from the bloodstream to the peripheral tissues, causing organ damage. This process is possible for their increased adherence and migration capacity mediated by adhesion molecules, such as CD44. Ten different variant isoforms of this molecule have been described, and two of them, CD44v3 and CD44v6 have been found to be increased on SLE T cells compared to healthy controls, being proposed as biomarkers of disease and disease activity. The process of alternative splicing of CD44 transcripts is not fully understood. We investigated the mRNA expression of CD44v3 and CD44v6 and also analyzed possible CD44 splicing regulators (ESRP1 molecule and rs9666607 CD44 polymorphism) in a cohort of SLE patients compared to healthy controls. Methods This study involved 18 SLE patients and 18 healthy controls. Total RNA and DNA were extracted by peripheral blood mononuclear cells. The expression study was conducted by quantitative RT-polymerase chain reaction, using SYBR Green protocol. Genotyping of rs9666607 SNP was performed by direct sequencing. Results CD44v6 mRNA expression was higher in SLE patients compared to healthy controls (p = 0.028). CD44v3/v6 mRNA ratio in healthy controls was strongly unbalanced towards isoform v3 compared to SLE patients (p = 0.002) and decreased progressively from healthy controls to the SLE patients in remission and those with active disease (p = 0.015). The expression levels of CD44v3 and CD44v6 mRNA correlated with the disease duration (p = 0.038, Pearson r = 0.493 and p = 0.038, Pearson r = 0.495, respectively). Splicing regulator ESRP1 expression positively correlated with CD44v6 expression in healthy controls (p = 0.02, Pearson r = 0.532) but not in SLE patients. The variant A allele of rs9666607 of CD44 was associated with higher level of global CD44 mRNA (p = 0.04) but not with the variant isoforms. Conclusions In SLE patients, the increase in CD44v6 protein correlates with a higher transcript level of this isoform, confirming an impairment of CD44 splicing in the disease, whose regulatory mechanisms require further investigation.

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