SAT0205 A MORE SPECIFIC INTEGRATED MODEL FOR IDENTIFYING BACTERIAL INFECTION IN SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1045-1046
Author(s):  
M. Feng ◽  
X. C. Zhao ◽  
J. Luo
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Bacterial Infection ◽  
Disease Activity ◽  
Sensitivity And Specificity ◽  
Lupus Erythematosus ◽  
Roc Curves ◽  
Systemic Lupus ◽  
Routine Examination ◽  
Tnf Α ◽  
Ifn Γ

Background:Systemic lupus erythematosus (SLE) is a multisystemic inflammatory disorder [1]. Given that immunosuppressive therapy is adopted as the predominant treatment option for SLE, up to half of SLE patients develop infections during their disease progress, and bacterial infection serves as the leading cause of morbidity and mortality in SLE patients [2]. Owing to the therapeutic regimen to bacterial infection and SLE flare are absolutely opposite, timely diagnosis and correct treatment are of vital importance, and improper treatment strategy may be fatal. No single biomarker, however, has exhibited sufficient sensitivity and specificity to serve as a standard tool for distinguishing bacterial infection from SLE flare.Objectives:To find a method by integrating cytokines, lymphocyte cells and routine examination biomarkers to observe its capacity for identifying bacterially infected SLE patients.Methods:Total 175 SLE patients (65 infected and 110 flare) were recruited into our study. The criteria of bacterial infection was positive isolation of bacteria, typical clinical symptoms and signs, imaging positive results and positive feedback on antibacterial treatment and lupus flare was regarded as three points higher than their previous SLEDAI. The disease activity of SLE patients was evaluated based on Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Lymphocyte cells (CD3+T, CD4+T, CD8+T, B, NK, Th1, Th2, Th17 and Treg) and cytokines [interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ) and IL-17] were measured by flow cytometry. Blood routine examination, erythrocyte sedimentation rate (ESR), C-Reactive Protein (CRP) Complement 3 (C3), C4, procalcitonin (PCT), immunoglobulin M (IgM), IgA and IgG were also evaluated. Partial least square discriminant analysis (PLS-DA) and supervised orthogonal PLS-DA (OPLS-DA) were applied to perform multivariate analysis of the data and further group the patients with bacterial infection. Receiver operating characteristic (ROC) curves were also plotted to investigate the ability of individual indicator and the combination of multiple indicators to identify bacterial infection.Results:The PLS-DA model showed a clear identification effect by the performance of R2Y=0.991 and Q2=0.970. The OPLS-DA model (R2Y=0.996 and Q2=0.991) exhibited a better separation of patients with bacterial infection. And the Observed vs. predicted plot of the OPLS-DA model demonstrated that all SLE patients were correctly separated into infected or flare groups, indicating that the model had a strong predictive ability for bacterial infection. For single indicator, infected patients had higher WBC, neutrophil (NEUT), ESR, CRP and PCT (P=0.002, 0.019, 0.002, <0.001, <0.001, respectively), and lower Treg cells (P=0.012). The levels of serum IL-6, IL-10, IFN-γ and TNF-α (P<0.001, =0.022, 0.014, 0.011, respectively) were significantly increased in infected group. ROC curves showed that the combination of the ten indicators showed the largest AUC and the highest accuracy, as well as balanced and relatively high sensitivity and specificity. Furthermore, the AUC of the combination was greatly higher than that of WBC, NEUT, ESR, CRP, PCT, Treg, IL-6, IL-10, IFN-γ and TNF-α (P<0.001).Conclusion:PLS-DA, OPLS-DA models including cytokines, lymphocyte cells and routine biomarkers and combination of WBC, NEUT, ESR, CRP, PCT, Treg, IL-6, IL-10, IFN-γ and TNF-α in ROC curve may be more predictive for finding bacterial infection in SLE and may prompt clinicians more promptly and accurately to help them make correct medication.References:[1]Illescas-Montes R, Corona-Castro CC, Melguizo-Rodríguez L, et al. Infectious processes and systemic lupus erythematosus. Immunology 2019;158:153-160.[2]Furst DE, Breedveld FC, Kalden JR, et al. Updated consensus statement on biological agents for the treatment of rheumatic diseases. Ann Rheum Dis 2002; 61: ii2–7.Disclosure of Interests:None declared

Expression of High Mobility Group Box Chromosomal Protein 1 and Its Modulating Effects on Downstream Cytokines in Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (4) ◽  
pp. 766-775 ◽  
Author(s):  
JIE LI ◽  
HONGFU XIE ◽  
TING WEN ◽  
HONGBO LIU ◽  
WU ZHU ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Messenger Rna ◽  
Activity Index ◽  
High Mobility ◽  
High Mobility Group ◽  
Chromosomal Protein ◽  
Systemic Lupus ◽  
Tnf Α

Objective.To compare the expression of high mobility group box chromosomal protein 1 (HMGB1) and the modulating effects on its downstream cytokines in patients with systemic lupus erythematosus (SLE) and healthy controls.Methods.HMGB1 concentrations in serum from SLE patients and controls were measured by immunoblot analysis. HMGB1 messenger RNA (mRNA) expression in peripheral blood mononuclear cells (PBMC) was detected by real-time reverse transcription–polymerase chain reaction. Immunofluorescence assay was employed to examine the translocation of HMGB1 in monocytes after endotoxin stimulation. Release of tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) by PBMC after rHMGB1 stimulation was also measured.Results.Serum HMGB1 levels and HMGB1 mRNA expressions in PBMC were elevated in SLE patients compared with controls. A positive correlation was demonstrated between HMGB1 concentrations and SLE Disease Activity Index. There was an inverse correlation between HMGB1 levels and C4 and C3 concentrations in SLE patients. HMGB1 concentrations were higher in patients with vasculitis and myositis. Lipopolysaccharide stimulated a temporarily elevated release of HMGB1 in SLE patients compared with controls. The pattern and localization of HMGB1 staining in monocytes were similar in both groups. After stimulation with rHMGB1, TNF-α level decreased but IL-6 level increased in SLE patients compared with controls.Conclusion.Our findings suggest that increased serum levels of HMGB1 in SLE may be associated with lupus disease activity. The altered production of TNF-α and IL-6 in response to rHMGB1 stimulation may participate in the disruption of cytokine homeostasis in SLE.

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.

Gene expression of cytokines (TNF-α, IFN-γ), serum profiles of IL-17 and IL-23 in paediatric systemic lupus erythematosus

Lupus ◽  
2012 ◽  
Vol 21 (10) ◽  
pp. 1105-1112 ◽  
Author(s):  
A Rana ◽  
RW Minz ◽  
R Aggarwal ◽  
S Anand ◽  
N Pasricha ◽  
...  
Keyword(s):  
Gene Expression ◽  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Tnf Α ◽  
Ifn Γ

scholarly journals Th cytokine profile in childhood-onset systemic lupus erythematosus

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Quan ◽  
Jingnan An ◽  
Gang Li ◽  
Guanghui Qian ◽  
Meifang Jin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Healthy Control Group ◽  
Control Group ◽  
Childhood Onset ◽  
Systemic Lupus ◽  
Healthy Control ◽  
Ifn Γ ◽  
Onset Systemic Lupus Erythematosus

Abstract Background Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to detect the serum levels of Th (T helper) cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α) in cSLE and healthy controls, and then to elucidate their association with clinical manifestations, disease activity and laboratory parameters. In order to provide clues for early diagnosis and timely intervention treatment of cSLE patients. Methods A total of 33 children with cSLE and 30 healthy children were enrolled in this study. Children in the cSLE group were classified into the inactive or active cSLE group according to their SLE disease activity index 2000 (SLEDAI-2 K) score. Th cytokine profiles in the peripheral blood were detected and analysed. Results Levels of IL-2, IL-10 and IL-21 in the cSLE group were significantly higher than those in the healthy control group (P < 0.05, P < 0.01 and P < 0.01, respectively). Expression of IL-2, IL-10 and IL-21 in the active cSLE group was significantly higher than that in the healthy control group (P < 0.05, P < 0.01 and P < 0.05, respectively), but that of IL-22 expression was markedly lower in the active cSLE group than in the healthy control group (P < 0.001). IL-21 in the inactive SLE group was significantly higher than that in the healthy control group (P < 0.05), and levels of IL-2 and IL-10 in the active cSLE group were significantly higher than those in the inactive cSLE group (P < 0.01 and P < 0.05). In-depth analysis showed that after excluding age, gender and drug interference, the levels of IL-2 (P < 0.05), IL-6 (P < 0.05) and IL-10 (P < 0.05) were still positively correlated with SLEDAI-2 K scores. However, the levels of IL-6 (P < 0.05) and IFN- γ (P < 0.05) were still negatively correlated with CD4+/CD8+, and the concentration of IL-6 (P < 0.05) was still positively correlated with the occurrence of nephritis. Conclusion This study provides a theoretical basis for the discovery of effective methods to regulate imbalance in T lymphocyte subsets in cSLE, which may lead to new approaches for the diagnosis of cSLE.

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 Identification of Peptides as Novel Inhibitors to Target IFN-γ, IL-3, and TNF-α in Systemic Lupus Erythematosus

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Ghulam Mustafa ◽  
Hafiza Salaha Mahrosh ◽  
Mahwish Salman ◽  
Sumaira Sharif ◽  
Raheela Jabeen ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Chronic Inflammatory Demyelinating Polyneuropathy ◽  
Protein Docking ◽  
Ligand Docking ◽  
Drug Candidate ◽  
Systemic Lupus ◽  
Binding Interactions ◽  
Tnf Α ◽  
Ifn Γ

Autoimmune disorder is a chronic immune imbalance which is developed through a series of pathways. The defect in B cells, T cells, and lack of self-tolerance has been greatly associated with the onset of many types of autoimmune complications including rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and chronic inflammatory demyelinating polyneuropathy. The SLE is an autoimmune disease with a common type of lupus that causes tissue and organ damage due to the wide spread of inflammation. In the current study, twenty anti-inflammatory peptides derived from plant and animal sources were docked as ligands or peptides counter to proinflammatory cytokines. Interferon gamma (IFN-γ), interleukin 3 (IL-3), and tumor necrosis factor alpha (TNF-α) were targeted in this study as these are involved in the pathogenesis of SLE in many clinical studies. Two docking approaches (i.e., protein-ligand docking and peptide-protein docking) were employed in this study using Molecular Operating Environment (MOE) software and HADDOCK web server, respectively. Amongst docked twenty peptides, the peptide DEDTQAMMPFR with S -score of -11.3018 and HADDOCK score of − 10.3 ± 2.5  kcal/mol showed the best binding interactions and energy validation with active amino acids of IFN-γ protein in both docking approaches. Depending upon these results, this peptide could be used as a potential drug candidate to target IFN-γ, IL-3, and TNF-α proteins to control inflammatory events. Other peptides (i.e., QEPQESQQ and FRDEHKK) also revealed good binding affinity with IFN-γ with S -scores of -10.98 and -10.55, respectively. Similarly, the peptides KHDRGDEF, FRDEHKK, and QEPQESQQ showed best binding interactions with IL-3 with S -scores of -8.81, -8.64, and -8.17, respectively.

Lupus band test for diagnostic evaluation in systemic lupus erythematosus

Lupus ◽  
2022 ◽  
pp. 096120332110664
Author(s):  
Chanidapa Wongtada ◽  
Stephen J Kerr ◽  
Pawinee Rerknimitr
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Sensitivity And Specificity ◽  
Lupus Erythematosus ◽  
Normal Skin ◽  
Characteristic Curve ◽  
Systemic Lupus ◽  
Clinically Normal ◽  
Activity Types ◽  
Lesion Skin

Background The lupus band test (LBT) using a sample of clinically normal skin was proposed as a useful diagnostic test for systemic lupus erythematosus (SLE). It is mostly performed to help diagnosing SLE in patients with insufficient clinical and serological profiles. However, most published studies on its utility are outdated and the results remain controversial. Objectives To determine the diagnostic performance of LBT on non-lesion sun-protected (NLSP) and sun-exposed (NLSE) skin for SLE. Methods Consecutively presenting patients with clinical and serological suspicion of SLE who had LBT performed on non-lesion skin during January 2012 to August 2021 were retrospectively studied. LBT performed on either NLSE or NLSP skin biopsies were all included. Laboratory characteristics, number, types and patterns of deposited immunoreactants and disease activity were also assessed. Results LBT was performed in 57 patients with suspected SLE. LBT was positive in 18/57, 9/28 and 6/21 patients in overall non-lesion, NLSE and NLSP, respectively. Of all patients, 23 patients were diagnosed with SLE and 34 patients with other diseases. Overall, the sensitivity and specificity of LBT on non-lesion skin was 56.5% and 88.2%, respectively. The ability of the test to discriminate between those with and without SLE, assessed by the area under the Receiver-Operating Characteristic curve, was 0.72 (0.61–0.84). The sensitivity and specificity of LBT on NLSE skin was 58.3% and 87.5% while those of NLSP skin, were 57.1% and 85.7%, respectively. We found no significant correlation between the positivity of LBT and overall disease activity. Types, number and pattern of deposited immunoreactants also showed no correlation with disease activity (all p > 0.05). Conclusions Used as a diagnostic adjunct, non-lesion LBT is still of value for diagnosing SLE in inconclusive cases.

Cytokines, 25-OH vit D and disease activity in patients with juvenile-onset systemic lupus erythematosus

Lupus ◽  
2020 ◽  
pp. 096120332097306
Author(s):  
Assem M Abo-Shanab ◽  
Shams Kholoussi ◽  
Rania Kandil ◽  
Dalia Dorgham
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Negative Correlation ◽  
Lupus Erythematosus ◽  
Laboratory Data ◽  
Damage Index ◽  
Systemic Lupus ◽  
Juvenile Onset ◽  
Ifn Γ ◽  
Onset Systemic Lupus Erythematosus

Background Juvenile onset systemic lupus erythematosus JO-SLE patients usually exhibit a more aggressive disease course compared to adult patients. Vitamin D deficiency is proposed to be associated with increased disease activity and flares of numerous autoimmune diseases like SLE, rheumatoid arthritis, and scleroderma. Objective To evaluate the level of IL-17, IFN-γ, and 25-OH Vit D in JO-SLE patients versus healthy controls, and determine the correlation of those inflammatory mediators with SLE disease activity and damage scores. Furthermore, to analyze the relationship between 25-OH Vit D levels with the inflammatory cytokines (IFN-γ and IL-17) in JO-SLE patients. Patients and methods Fifty JO-SLE patients and 25 controls were included in this study. Clinical and laboratory data of patients at the time of the study were recorded. SLE disease activity and damage were assessed using the SLEDAI-2K disease score and SLICC damage index, respectively. Plasma 25-OH Vit D, IFN-γ, and IL-17 concentrations were determined using the human ELISA kit. Results Plasma 25-OH Vit D levels (20 ng/mL) were significantly lower in JO-SLE patients compared to (31 ng/mL) controls (P = 0.014). Plasma levels of IFN-γ and IL-17 were significantly higher (163.5 and 25.5 pg./mL) in JO-SLE patients than (68.3 and 3 pg./mL) that of controls (P = 0.016 and P = 0.013). There was a significant negative correlation between 25-OH Vit D levels and SLEDAI-2K (R= -0.431) as well as IFN-γ (R= -0.471) plasma level (P = 0.022 and P = 0.027). Conclusion IFN-γ and IL-17 were significantly higher in JO-SLE patients, while 25-OH Vit D was significantly lower compared to controls. There was a negative correlation between 25-OH Vit D and each of SLEDAI-2K and IFN-γ.

scholarly journals Cytokines, Autoantibodies, and Complements in Active Systemic Lupus Erythematosus Patients from Javanese Population

2020 ◽  
Vol 26 (3) ◽  
Author(s):  
Yuliasih Yuliasih ◽  
Lita Diah Rahmawati ◽  
Putu Ayu Niken Amrita ◽  
Setiati Widyaningrum ◽  
Dodi Kriswanto
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Clinical Manifestations ◽  
Systemic Lupus ◽  
Genetic Traits ◽  
American College Of Rheumatology ◽  
Acr Criteria ◽  
Tnf Α ◽  
Spearman’S Correlation

Systemic Lupus Erythematosus (SLE) is an autoimmune disease that has various clinical manifestations. The SLE pathogenesis involves both innate and adaptive immunological components. The system is essentially determined by genetic factors that control certain clinical and serological manifestations. Genetic traits that determine the roles of cytokines, autoantibodies, and complements in SLE vary among ethnicities. The roles of TNF-α, IL-6, anti-C1q, anti-dsDNA, C3, and C4 towards SLE activity need to be evaluated in the Javanese population. This study aimed to determine the correlation of TNF-α, IL-6, anti-C1q antibodies, anti-dsDNA, C3, and C4 with SLE activity. Forty SLE patients were diagnosed based on the American College of Rheumatology (ACR) criteria. Disease activity was measured by the Systemic Lupus Activity Measure (SLAM) index. TNF-α, IL-6, Anti-C1q, and anti-dsDNA levels were measured by ELISA, while MINIMEPH measured C3 and C4. Thirty-nine female and one male patient with SLE were diagnosed according to ACR criteria. The mean of SLAM score, anti-dsDNA, C3, and C4 levels was 20.98±6.7, 224.96±298.6, 68.70±37.08 mg/dL, and 18.75±10.69 mg/dL, respectively. Spearman's correlation test showed a positive correlation between TNF-α (r = 0.971, p<0.001), IL-6 (r=0.835, p<0.001), anti-C1q (r=0.399, p=0.01), and disease activity (SLAM score) by using. The linear regression test for TNF-α, IL-6, anti-C1q, and SLAM showed the strongest association for TNF-α (r=0.891, p<0.000). TNF-α, IL-6, and anti-C1q were correlated to disease activity in SLE patients from the Javanese population.

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