scholarly journals Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement and SLE disease activity

2020 ◽  
Author(s):  
Mingjiao Zhang ◽  
Hongyu Jie ◽  
Yong Wu ◽  
Xinai Han ◽  
Xing Li ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Characteristic Curve ◽  
Mrna Level ◽  
Renal Involvement ◽  
Area Under The Curve ◽  
Peripheral Blood Mononuclear ◽  
Autoantibody Production ◽  
Regulated Necrosis

Abstract Background: Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis, however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE. Methods: Real-time transcription-polymerase chain reaction analysis (RT-PCR) was used to determine expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA) and 30 age- and sex-matched healthy controls(HC). Spearman's correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic curve (ROC) was created to evaluate the diagnostic value. Results: Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for anti-nuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r=0.3577, p=0.0237), erythrocyte sedimentation rate (ESR) (r=0.4091, p=0.0043), serum immunoglobulin G (IgG) concentration (r=0.3546, p=0.0289) and the numbers of positive antinuclear antibodies (ANAs) (r=0.3945, p=0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779 - 0.9775, p<0.001) to discriminate SLE from controls.Conclusions: These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.

scholarly journals Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement and SLE disease activity

2020 ◽  
Author(s):  
Mingjiao Zhang ◽  
Hongyu Jie ◽  
Yong Wu ◽  
Xinai Han ◽  
Xing Li ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Characteristic Curve ◽  
Mrna Level ◽  
Renal Involvement ◽  
Area Under The Curve ◽  
Peripheral Blood Mononuclear ◽  
Autoantibody Production ◽  
Regulated Necrosis

Abstract Background Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis, however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE. Methods Real-time transcription-polymerase chain reaction analysis (RT-PCR) was used to determine expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA) and 30 age- and sex-matched healthy controls(HC). Spearman's correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic curve (ROC) was created to evaluate the diagnostic value. Results Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for anti-nuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r = 0.3577, p = 0.0237), erythrocyte sedimentation rate (ESR) (r = 0.4091, p = 0.0043), serum immunoglobulin G (IgG) concentration (r = 0.3546, p = 0.0289) and the numbers of positive antinuclear antibodies (ANAs) (r = 0.3945, p = 0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779–0.9775, p < 0.001) to discriminate SLE from controls. Conclusions These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.

scholarly journals Increased MLKL mRNA level in the PBMCs is correlated with autoantibody production, renal involvement, and SLE disease activity

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Mingjiao Zhang ◽  
Hongyu Jie ◽  
Yong Wu ◽  
Xinai Han ◽  
Xing Li ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Antinuclear Antibodies ◽  
Mononuclear Cells ◽  
Mrna Level ◽  
Renal Involvement ◽  
Pcr Analysis ◽  
Peripheral Blood Mononuclear ◽  
Autoantibody Production ◽  
Regulated Necrosis

Abstract Background Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis; however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE. Methods Real-time transcription-polymerase chain reaction (RT-PCR) analysis was used to determine the expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA), and 30 age- and sex-matched healthy controls (HC). Spearman’s correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value. Results Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for antinuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r = 0.3577, p = 0.0237), erythrocyte sedimentation rate (ESR) (r = 0.4091, p = 0.0043), serum immunoglobulin G (IgG) concentration (r = 0.3546, p = 0.0289), and the numbers of positive antinuclear antibodies (ANAs) (r = 0.3945, p = 0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779–0.9775, p < 0.001) to discriminate SLE from controls. Conclusions These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.

scholarly journals Association between peripheral blood mononuclear cell ORMDL3 expression and the asthma predictive index in preschool children

2019 ◽  
Vol 47 (8) ◽  
pp. 3727-3736 ◽  
Author(s):  
Yaqin Li ◽  
Lanfang Cao ◽  
Qing Yu ◽  
Haiyan Xue ◽  
Yanming Lu
Keyword(s):  
Risk Factors ◽  
Preschool Children ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immunoglobulin E ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
House Dust Mites ◽  
Predictive Index ◽  
Peripheral Blood Mononuclear

Objective This study aimed to assess whether orosomucoid 1-like 3 (ORMDL3) expression and environmental and clinical factors are associated with wheezing episodes in preschool children. Methods Children diagnosed with wheezing episodes were classified according to their asthma predictive index (API) in the past year as follows: API+ (≥4 wheezing episodes), API− (1–3 wheezing episodes), and API0 (without wheezing). ORMDL3 expression was assessed by real-time polymerase chain reaction in peripheral blood mononuclear cells (PBMCs). Receiver operating characteristic curve analysis of ORMDL3 expression and the API was performed for diagnosing wheezing episodes. Correlations between ORMDL3 expression and asthma risk factors were examined using Spearman’s correlation. Results PBMC ORMDL3 expression was higher in the API+ group compared with the API− and API0 groups. The area under the curve for ORMDL3 expression was 0.820 (95% confidence interval, 0.771–0.869). ORMDL3 expression was positively correlated with the API ( r = 0.447), infantile eczema ( r = 0.499), wheezing ( r = 0.516), total immunoglobulin E ( r = 0.208), and environmental factors, including Dermatophagoides pteronyssinus ( r = 0.357), house dust mites ( r = 0.112), dog fur ( r = 0.226), and Aspergillus( r = 0.257). ORMDL3 expression was negatively correlated with amaranth ( r = −0.122). Conclusions ORMDL3 expression in PBMCs is positively associated with the API and some asthma-related clinical and environmental risk factors in preschoolers.

scholarly journals CD4+CD45RA−FOXP3low Regulatory T Cells as Potential Biomarkers of Disease Activity in Systemic Lupus Erythematosus Brazilian Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Helena L. Silva-Neta ◽  
Maria C. A. Brelaz-de-Castro ◽  
Mardonny B. O. Chagas ◽  
Henrique A. Mariz ◽  
Rodrigo G. de Arruda ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Linear Regression ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Foxp3 Expression ◽  
Treg Cells ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear ◽  
Potential Biomarkers

Heren, we analyzed Treg cells as potential biomarkers of disease activity in systemic lupus erythematosus (SLE) patients. Peripheral blood mononuclear cells from 30 SLE patients (15 active: SLEDAI > 6/15 SLE remission: SLEDAI< 6) and 15 healthy volunteers were purified. Treg immunophenotyping was performed using CD4, CD25, CD45, CD127, and FOXP3 markers. CD4+FOXP3+ Treg activation state was investigated based on CD45RA and FOXP3 expression. To increase the accuracy of our findings, a multivariate linear regression was performed. We showed a significant increase in the frequency of CD4+FOXP3+ Treg cells in SLE patients. However, unlike all other Treg cells phenotypes analyzed, only eTreg (CD4+FOXP3highCD45RA-) (p=0.01) subtype was inversely correlated with disease activity while Foxp3+nontreg (CD4+FOXP3lowCD45RA-) (p=0.003) exerted a direct influence in the outcome of the disease. Foxp3+nontreg cells were the most consistent SLE active indicator, confirmed by multiple linear regression analyses. In summary, our results demonstrate Foxp3+nontreg cells as new biomarkers in the search of an effective therapeutic strategy in SLE.

Sign in / Sign up

Export Citation Format

Share Document