scholarly journals Development of Prediction Models for New Integrated Models and a Bioscore System to Identify Bacterial Infections in Systemic Lupus Erythematosus

2021 ◽  
Vol 11 ◽  
Author(s):  
Xvwen Zhai ◽  
Min Feng ◽  
Hui Guo ◽  
Zhaojun Liang ◽  
Yanlin Wang ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Bacterial Infections ◽  
Prediction Models ◽  
Predictive Ability ◽  
Treg Cells ◽  
Interferon Γ ◽  
Systemic Lupus ◽  
Ifn Γ ◽  
Factor Α

ObjectivesDistinguishing flares from bacterial infections in systemic lupus erythematosus (SLE) patients remains a challenge. This study aimed to build a model, using multiple blood cells and plasma indicators, to improve the identification of bacterial infections in SLE.DesignBuilding PLS-DA/OPLS-DA models and a bioscore system to distinguish bacterial infections from lupus flares in SLE.SettingDepartment of Rheumatology of the Second Hospital of Shanxi Medical University.ParticipantsSLE patients with flares (n = 142) or bacterial infections (n = 106) were recruited in this retrospective study.OutcomeThe peripheral blood of these patients was collected by the experimenter to measure the levels of routine examination indicators, immune cells, and cytokines. PLS-DA/OPLS-DA models and a bioscore system were established.ResultsBoth PLS-DA (R2Y = 0.953, Q2 = 0.931) and OPLS-DA (R2Y = 0.953, Q2 = 0.942) models could clearly identify bacterial infections in SLE. The white blood cell (WBC), neutrophile granulocyte (NEUT), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), IL-10, interferon-γ (IFN-γ), and tumor necrosis factor α (TNF-α) levels were significantly higher in bacteria-infected patients, while regulatory T (Treg) cells obviously decreased. A multivariate analysis using the above 10 dichotomized indicators, based on the cut-off value of their respective ROC curve, was established to screen out the independent predictors and calculate their weights to build a bioscore system, which exhibited a strong diagnosis ability (AUC = 0.842, 95% CI 0.794–0.891). The bioscore system showed that 0 and 100% of SLE patients with scores of 0 and 8–10, respectively, were infected with bacteria. The higher the score, the greater the likelihood of bacterial infections in SLE.ConclusionsThe PLS-DA/OPLS-DA models, including the above biomarkers, showed a strong predictive ability for bacterial infections in SLE. Combining WBC, NEUT, CRP, PCT, IL-6, and IFN-γ in a bioscore system may result in faster prediction of bacterial infections in SLE and may guide toward a more appropriate, timely treatment for SLE.

Overexpression of interferon-γ and indoleamine 2, 3-dioxygenase in systemic lupus erythematosus: relationship with the disease activity

2017 ◽  
Vol 41 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Saeed Mohammadi ◽  
Sima Sedighi ◽  
Ali Memarian ◽  
Yaghoub Yazdani
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Interferon Γ ◽  
Systemic Lupus ◽  
Indoleamine 2 ◽  
Ifn Γ ◽  
Positive Correlations

AbstractBackground:Indoleamine 2, 3-dioxygenase (IDO) is a tryptophan catabolizing enzyme which is involved in immune regulation and autoimmune disorders such as systemic lupus erythematosus (SLE). Interferon-γ (IFN-γ) is an inflammatory cytokine which is the major inducer of IDO expression. Here, we evaluated the level of IFN-γ and IDO among SLE patients in correlation with the severity of SLE.Methods:Fifty-three SLE patients and 35 age matched healthy donors were enrolled in this study. Systemic lupus erythematosus disease activity index (SLEDAI) was used to calculate the disease activity. Real-time RT-PCR and ELISA were used to evaluate the gene expression of IDO and IFN-γ plasma concentration, respectively.Results:We showed that IDO-1, IDO-2 and IFN-γ were overexpressed among SLE patients significantly (p<0.0001). There were significant positive correlations between IFN-γ with the expression of IDO-1 (r=0.722, p<0.0001) and IDO-2 (r=0.682, p<0.0001). There were also positive correlations between SLEDAI scores with IDO-1 (r=0.675, p<0.0001), IDO-2 (r=0.727, p<0.0001) and IFN-γ (r=0.907, p<0.0001).Conclusions:IDO expression and IFN-γ level could be introduced as helpful biomarkers for the determination of disease severity in SLE patients.

scholarly journals Double-Edged Sword: Interleukin-2 Promotes T Regulatory Cell Differentiation but Also Expands Interleukin-13- and Interferon-γ-Producing CD8+ T Cells via STAT6-GATA-3 Axis in Systemic Lupus Erythematosus

2021 ◽  
Vol 12 ◽  
Author(s):  
Hiroshi Kato ◽  
Andras Perl
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Lupus Erythematosus ◽  
Interleukin 2 ◽  
Inflammatory Cells ◽  
Interferon Γ ◽  
T Regulatory Cell ◽  
Systemic Lupus ◽  
Double Positive ◽  
Ifn Γ

Interleukin-2 (IL-2) expands the depleted T regulatory (Treg) cell population, and it has emerged as a potential therapy in systemic lupus erythematosus (SLE). However, IL-2 administration may involve the risk of expanding unwanted pro-inflammatory cells. We herein studied the effects of IL-2 on pro-inflammatory cytokine production by CD4+ and CD8+ T cells in parallel with Treg development following CD3/CD28 co-stimulation. While Treg cells are depleted in SLE patients, their CD4+ T cells were poised to receive and activate IL-2 signaling as evidenced by upregulation of CD25 and enhanced IL-2-incued STAT5 phosphorylation during Treg differentiation. In patients with SLE, however, IL-2 also expanded CD8+ T cells capable of producing interleukin-5, interkeukin-13 (IL-13), and interferon-γ (IFN-γ) that occurred with enhanced expression of GATA-3 and phosphorylation of STAT6 but not STAT5. Our data pinpoint a safety signal for systemic administration of IL-2 and challenges a long-held conceptual platform of type 1 and 2 cytokine antagonism by newly documenting the IL-2-dependent development of IL-13 and IFN-γ double-positive (IL-13+IFNγ+) CD8+ T cells in SLE.

scholarly journals Sjögren Syndrome in Systemic Lupus Erythematosus: A Subset Characterized by a Systemic Inflammatory State

2019 ◽  
Vol 47 (6) ◽  
pp. 865-875 ◽  
Author(s):  
Guillermo Ruacho ◽  
Marika Kvarnström ◽  
Agneta Zickert ◽  
Vilija Oke ◽  
Johan Rönnelid ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Proinflammatory Cytokines ◽  
Lupus Erythematosus ◽  
Interferon Γ ◽  
Sjögren Syndrome ◽  
Sjogren Syndrome ◽  
Systemic Lupus ◽  
American College Of Rheumatology ◽  
Inflammatory State ◽  
Factor Α

Objective.An often-neglected subset of patients with systemic lupus erythematosus (SLE) is those with secondary Sjögren syndrome (SLE-sSS). Further, primary SS overlaps and can be difficult to delineate from SLE. To shed light on the SLE-sSS subset, we investigated a large and well-characterized SLE cohort, comparing patients with SLE-sSS and SLE patients without SS (SLE-nonsSS) and controls.Methods.We included 504 consecutive patients with SLE, fulfilling the 1982 revised American College of Rheumatology criteria, and 319 controls from the general population, matched for age and sex to the first 319 patients. SLE-sSS was defined according to the American-European Consensus Criteria (AECC). A thorough clinical examination, including subjective and objective quantifications of sicca symptoms, was performed in all participants. Autoantibodies and 20 selected cytokines were measured by luminex and multiplex analysis, respectively.Results.SLE-sSS, as defined by AECC, occurred in 23% of the patients with SLE. In comparison to SLE-nonsSS, the SLE-sSS group was older and more frequently female. Leukopenia and peripheral neuropathy were more frequent and nephritis less frequent. Circulating levels of 6/20 investigated proinflammatory cytokines [tumor necrosis factor-α, interleukin (IL) 6, monocyte chemoattractant protein 4, macrophage inflammatory protein 1β, IL-12/IL-23p40, and interferon γ–induced protein 10], total IgG, anti-SSA/Ro52, anti-SSA/Ro60, anti-SSB/La antibodies, and rheumatoid factor (IgM and IgA) were higher in the SLE-sSS group (p < 0.05 for all comparisons).Conclusion.The frequency of SLE-sSS increased with age and affected roughly one-quarter of all patients with SLE. Despite less internal organ involvement, a systemic inflammatory state with high levels of proinflammatory cytokines is present in the SLE-sSS subgroup. This is a novel observation that may affect future understanding and treatment of the SLE-sSS subset.

Increased CD4+CD25-Foxp3+ T cells in Chinese systemic lupus erythematosus: correlate with disease activity and organ involvement

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2057-2068 ◽  
Author(s):  
Z-J Yin ◽  
B-M Ju ◽  
L Zhu ◽  
N Hu ◽  
J Luo ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Cell Subset ◽  
Treg Cells ◽  
Organ Involvement ◽  
Systemic Lupus ◽  
Clinical Indicators ◽  
Disease States

Objective The increment of CD4+CD25−Foxp3+T cells has been reported in systemic lupus erythematosus (SLE) patients. However, the exact identity of this T cell subset is still unclear. Thus, we analyzed CD4+CD25−Foxp3+T cells and Treg cells (CD4+CD25+Foxp3+ T cells) in a large sample of Chinese SLE patients in different disease states. Methods A total of 280 SLE patients and 38 healthy volunteers were enrolled, which included 21 patients with untreated new-onset lupus (UNOL), 13 patients with drug withdrawal more than 6 months and 246 patients with treatments. Phenotypic and functional analysis of peripheral blood CD4+CD25−Foxp3+ T cells and Treg cells were performed by flow cytometry. The correlation of CD4+CD25−Foxp3+T cells and Treg cells with disease activity, clinical indicators and organ involvement were analyzed. Results CD4+CD25−Foxp3+ T cells and Treg cells were significantly increased in SLE patients and showed significantly positive correlations with disease activity. CD4+CD25−Foxp3+ T cells were significantly increased in patients with skin and hematologic involvement as well as arthritis. Diverse changes between CD4+CD25−Foxp3+ T cells and Treg cells when faced with different medications, especially HCQ and MMF. CD4+CD25−Foxp3+ T cells expressed more IFN-γ and less CTLA-4 than CD4+CD25+Foxp3+ T cells, which were similar to CD4+CD25+Foxp3− T cells, and expressed similar IL-17, ICOS and Helios to CD4+CD25+Foxp3+ T cells. The synthesis capacity of IL-10 of CD4+CD25−Foxp3+ T cells and the expression of GITR on CD4+CD25−Foxp3+ T cells were between CD4+CD25+Foxp3+ and CD4+CD25+Foxp3− T cells. Conclusions Our results indicate that increased CD4+CD25−Foxp3+ T cells in lupus patients, which combined the features of suppression and pro-inflammatory, may serve as a biomarker for disease activity and organ involvement in SLE.

C-reactive Protein Is a More Sensitive and Specific Marker for Diagnosing Bacterial Infections in Systemic Lupus Erythematosus Compared to S100A8/A9 and Procalcitonin

2012 ◽  
Vol 39 (4) ◽  
pp. 728-734 ◽  
Author(s):  
HYOUN-AH KIM ◽  
JA-YOUNG JEON ◽  
JEONG-MI AN ◽  
BO-RAM KOH ◽  
CHANG-HEE SUH
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Bacterial Infections ◽  
Area Under The Curve ◽  
Specific Marker ◽  
Operating Characteristics ◽  
C Reactive Protein ◽  
Systemic Lupus ◽  
Serum Samples ◽  
Reactive Protein

Objective.C-reactive protein (CRP), S100A8/A9, and procalcitonin have been suggested as markers of infection in patients with systemic lupus erythematosus (SLE). We investigated the clinical significance of these factors for indication of infection in SLE.Methods.Blood samples were prospectively collected from 34 patients with SLE who had bacterial infections and 39 patients with SLE who had disease flares and no evidence of infection. A second set of serum samples was collected after the infections or flares were resolved.Results.CRP levels of SLE patients with infections were higher than those with flares [5.9 mg/dl (IQR 2.42, 10.53) vs 0.06 mg/dl (IQR 0.03, 0.15), p < 0.001] and decreased after the infection was resolved. S100A8/A9 and procalcitonin levels of SLE patients with infection were also higher [4.69 μg/ml (IQR 2.25, 12.07) vs 1.07 (IQR 0.49, 3.05) (p < 0.001) and 0 ng/ml (IQR 0–0.38) vs 0 (0–0) (p < 0.001), respectively]; these levels were also reduced once the infection disappeared. In the receiver-operating characteristics analysis of CRP, S100A8/A9, and procalcitonin, the area under the curve was 0.966 (95% CI 0.925–1.007), 0.732 (95% CI 0.61–0.854), and 0.667 (95% CI 0.534–0.799), respectively. CRP indicated the presence of an infection with a sensitivity of 100% and a specificity of 90%, with a cutoff value of 1.35 mg/dl.Conclusion.Our data suggest that CRP is the most sensitive and specific marker for diagnosing bacterial infections in SLE.

scholarly journals Tumor Necrosis Factor-α Antagonist Etanercept Decreases Blood Pressure and Protects the Kidney in a Mouse Model of Systemic Lupus Erythematosus

Hypertension ◽  
2010 ◽  
Vol 56 (4) ◽  
pp. 643-649 ◽  
Author(s):  
Marcia Venegas-Pont ◽  
Michaele B. Manigrasso ◽  
Samira C. Grifoni ◽  
Babbette B. LaMarca ◽  
Christine Maric ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Blood Pressure ◽  
Tumor Necrosis Factor ◽  
Mouse Model ◽  
Lupus Erythematosus ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Systemic Lupus ◽  
Factor Α ◽  
Necrosis Factor

scholarly journals Correlations of Expression Levels of a Panel of Genes (IRF5, STAT4, TNFSF4, MECP2, and TLR7) and Cytokine Levels (IL-2, IL-6, IL-10, IL-12, IFN-γ, and TNF-α) with Systemic Lupus Erythematosus Outcomes in Jordanian Patients

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Amal H. Uzrail ◽  
Areej M. Assaf ◽  
Shtaywy S. Abdalla
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Renal Damage ◽  
Organ Damage ◽  
Systemic Lupus ◽  
Expression Levels ◽  
Cardiovascular Damage ◽  
Tnf Α ◽  
Cytokine Levels ◽  
Ifn Γ

Systemic lupus erythematosus (SLE) is characterized by systemic end-organ damage. We investigated the involvement of IRF5, TLR-7, MECP2, STAT4, and TNFSF4 genes and TNF-α, IFN-γ, IL-2, IL-12, IL-6, and IL-10 cytokines in SLE pathogenesis and in organ damage in Jordanian patients. Blood was collected from 51 patients and 50 controls. Expression levels of SLE genes in PBMCs and cytokine levels were determined using RT-PCR and ELISA, respectively. Expression levels of all genes and levels of TNF-α, IL-12, IL-6, and IL-10 were higher in SLE patients than those in controls (p<0.05), whereas IL-2 level was lower. High STAT4 (α), TNFSF4, and IL-10 levels correlated with cardiovascular damage, and high MECP2 (α) and TNF-α correlated with renal damage. Pulmonary and musculoskeletal damages correlated with high levels of TNFSF4. We concluded that STAT4 and TNFSF4 genes with TNF-α and IL-10 cytokines could be used as biomarkers to assess SLE activity and manage treatment.

scholarly journals The combination of polymorphisms within interferon-γ receptor 1 and receptor 2 associated with the risk of systemic lupus erythematosus

FEBS Letters ◽  
1999 ◽  
Vol 453 (1-2) ◽  
pp. 187-190 ◽  
Author(s):  
Hitoshi Nakashima ◽  
Hisako Inoue ◽  
Mitsuteru Akahoshi ◽  
Yosuke Tanaka ◽  
Kunihiro Yamaoka ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Interferon Γ ◽  
Systemic Lupus

scholarly journals Brief Report: Large-scale analysis of tumor necrosis factor α levels in systemic lupus erythematosus

2012 ◽  
Vol 64 (9) ◽  
pp. 2947-2952 ◽  
Author(s):  
Corinna E. Weckerle ◽  
Dorothy Mangale ◽  
Beverly S. Franek ◽  
Jennifer A. Kelly ◽  
Marissa Kumabe ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Tumor Necrosis ◽  
Large Scale ◽  
Tumor Necrosis Factor Α ◽  
Scale Analysis ◽  
Systemic Lupus ◽  
Large Scale Analysis ◽  
Factor Α ◽  
Necrosis Factor
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