scholarly journals A Role for Receptor-Interacting Protein Kinase-1 in Neutrophil Extracellular Trap Formation in Patients with Systemic Lupus Erythematosus: a Preliminary Study

2018 ◽  
Vol 45 (6) ◽  
pp. 2317-2328 ◽  
Author(s):  
Ruru Guo ◽  
Yang Tu ◽  
Shaowei Xie ◽  
Xue song Liu ◽  
Yang Song ◽  
...  
Keyword(s):  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Peripheral Blood Leukocytes ◽  
Systemic Lupus ◽  
Blood Leukocytes ◽  
Interacting Protein ◽  
Tnf Α ◽  
Ifn Γ

Background/Aims: Neutrophil extracellular traps (NETs) are known to play an important role in systemic lupus erythematosus (SLE) by triggering innate and adaptive immune responses. The molecular mechanisms responsible for their formation in SLE are still unclear. In this study, we aim to characterize the role of the receptor-interacting protein kinase-1 (RIPK1), a homologous serine/threonine kinase previously implicated in the regulation of necroptosis and tissue injury, in decreasing neutrophil death and formation of NETs, and to investigate the clinical implications of RIPK1 in SLE. Methods: Patients with SLE (n = 50) and healthy donors (n = 35) were enrolled in in vitro studies. Management of SLE patients was evaluated using the SLE disease activity index 2000 (SLEDAI-2K) score and laboratory variables. The mRNA level of RIPKs was measured by quantitative polymerase chain reaction (qPCR). Intracellular RIPK1 and RIPK3 production by peripheral blood leukocytes was detected by four-color flow cytometry and confirmed by automatic western blotting. TNF-α, IFN-γ, IL-1β, IL-2, IL-8, IL-18, and RIPK1 were measured by enzyme-linked immunosorbent assay. Cell death was assayed by Sytox green dye from peripheral neutrophils stimulated by RIPK-1-stabilizer necrostatin-1 (nec-1) and phorbol 12-myristate 13-acetate (PMA). Immunofluorescence staining and confocal microscopy were used to detect NET formation ex vivo. Quantification of NETs was determined by fluorescence spectrometry. Results: IFN-γ, IL-1β, IL-8, and IL-18 levels in serum were increased in SLE patients compared to controls. However, the expression of TNF-α, IL-2, and RIPK1 were decreased. In addition, we observed significant differences in the expression of RIPK1 in peripheral blood leukocytes. Of all the leukocytes, RIPK1 expression was significantly lower in neutrophils. Furthermore, we studied NETs formation in neutrophils of SLE with decreased RIPK1 expression, and these show increased susceptibility to NETosis, when stimulated with PMA and/or nec-1. Importantly, RIPK1 expression in neutrophils negatively correlated with ESR, CRP, 24-hour urine total protein, and the disease activity index in SLE. Conclusion: These data represent the first report of decreased RIPK1 expression in neutrophils of SLE patients and imply that RIPK1 may be involved in neutrophil death and NET formation. We suggest that RIPK1 is a potential biomarker to predict disease activity.

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.

CD4+CD28null T cells are expanded in moderately active systemic lupus erythematosus and secrete pro-inflammatory interferon gamma, depending on the Disease Activity Index

Lupus ◽  
2020 ◽  
Vol 29 (7) ◽  
pp. 705-714
Author(s):  
Agata Kosmaczewska ◽  
Lidia Ciszak ◽  
Malgorzata Stosio ◽  
Aleksandra Szteblich ◽  
Marta Madej ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Disease Activity ◽  
Interferon Gamma ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Immunosuppressive Treatment ◽  
Disease Activity Index ◽  
Systemic Lupus ◽  
Ifn Γ

Background Pathogenic CD4+CD28null cells are characterized by inflammatory cytokine synthesis and tropism to the inflamed tissues. Recent studies showed the involvement of CD28null T cells in a severe clinical outcome of lupus. However, their role in moderately active disease is still unresolved. Methods We examined the levels of circulating CD4+CD28null cells and CD8+CD28null suppressor T cells. We also compared the CD4+CD28null and CD4+CD28+ T-cell functional properties, including the expression of interferon gamma (IFN-γ) and Ki67 among systemic lupus erythematosus (SLE) patients ( n = 20) and healthy controls ( n = 20). All the patients were under immunosuppressive treatment and exhibited moderate SLE activity (median SLE Disease Activity Index (SLEDAI) = 6). Results In patients, we found elevated CD4+CD28null and unchanged levels of suppressor CD8+CD28null T cells. There was no difference between patients and controls in IFN-γ and Ki67-expressing CD4+, CD4+CD28+, and CD4+CD28null T cells, except for higher IFN-γ levels in CD4+CD28+ T cells in SLE. In each studied group, we observed a higher preponderance of IFN-γ- and Ki67-expressing cells among CD4+CD28null T cells and lower levels of IFN-γ in CD4+CD28null T cells compared to the CD28+ subset. Similarly, Ki67 intensity was decreased in healthy CD4+CD28null cells, whereas in patients, comparably high expression was observed in both subsets. IFN-γ intensity in CD4+CD28null T cells correlated with SLEDAI. Conclusion SLE with a moderately active clinical course is characterized by peripheral blood expansion of CD4+CD28null T cells and a normal abundance of suppressor CD8+CD28null T cells. The demonstration that these pathogenic CD4+ T cells, despite the lack of CD28, maintain the ability to produce pro-inflammatory IFN-γ positively correlated with disease activity as well as relatively high proliferative capacity may suggest their potentially predictive role in SLE flares.

Impact of markers of endothelial injury and hypercoagulability on systemic lupus erythematosus

Lupus ◽  
2020 ◽  
Vol 29 (2) ◽  
pp. 182-190
Author(s):  
W Batista Cicarini ◽  
R C Figueiredo Duarte ◽  
K Silvestre Ferreira ◽  
C de Mello Gomes Loures ◽  
R Vargas Consoli ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Endothelial Injury ◽  
Control Group ◽  
Systemic Lupus ◽  
Low Concentrations ◽  
The Relationship

We have explored the relationship between possible hemostatic changes and clinical manifestation of the systemic lupus erythematosus (SLE) as a function of greater or lesser disease activity according to Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) criteria. Endothelial injury and hypercoagulability were investigated in patients with SLE by measuring thrombomodulin (TM), D-dimer (DDi) and thrombin generation (TG) potential. A total of 90 participants were distributed into three groups: 1) women with SLE presenting with low disease activity (laSLE) (SLEDAI-2K ≤ 4), 2) women with SLE presenting with moderate to high disease activity (mhaSLE) (SLEDAI-2K > 4), and 3) a control group comprising healthy women. Levels of TM and DDi were higher both in the laSLE and mhaSLE groups compared to controls and in mhaSLE compared to the laSLE group. With respect to TG assay, lagtime and endogen thrombin potential, low concentrations of tissue factor provided the best results for discrimination among groups. Analysis of these data allow us to conclude that TM, DDi and TG are potentially useful markers for discriminating patients with very active from those with lower active disease. Higher SLE activity may cause endothelial injury, resulting in higher TG and consequently a hypercoagulability state underlying the picture of thrombosis common in this inflammatory disease.

scholarly journals Disease activity index is associated with subclinical atherosclerosis in childhood-onset systemic lupus erythematosus

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Priscila B. S. Medeiros ◽  
Roberta G. Salomão ◽  
Sara R. Teixeira ◽  
Diane M. Rassi ◽  
Luciana Rodrigues ◽  
...  
Keyword(s):  
Risk Factors ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Subclinical Atherosclerosis ◽  
Disease Activity Index ◽  
Uncontrolled Hypertension ◽  
Childhood Onset ◽  
Systemic Lupus

Abstract Background Systemic lupus erythematosus (SLE) is an independent risk factor for cardiovascular events. The present study determined the prevalence of subclinical atherosclerosis in childhood-onset SLE using the carotid intima-media thickness (CIMT) measurement and investigated associations between traditional and nontraditional risk factors for atherosclerosis, such as medications, SLE Disease Activity Index - SLEDAI-2 K and SLICC-ACR damage index and CIMT. Methods Cross-sectional prospective study between 2017 and 2018. CIMT was assessed by ultrasonography. Data were collected by chart review, nutritional evaluation and laboratory tests and analyzed by Fisher, Wilcoxon-Mann-Whitney tests, multiple linear and log binomial regression. Results Twenty-eight patients (mean age 13.9 years, SD 3) were enrolled. The prevalence of subclinical atherosclerosis was 32% (95% CI 14.8, 49.4). The mean CIMT was 0.43 ± 0.035 mm. The most common traditional risk factors observed were dyslipidemia (82.1%), uncontrolled hypertension (14.2%), obesity (14.3%), and poor diet (78.6%). Uncontrolled hypertension (p = 0.04), proteinuria (p = 0.02), estimated glomerular filtration rate < 75 ml /min/1.73 m2 (p = 0.02) and SLEDAI-2 K > 5 (P = 0.04) were associated with subclinical atherosclerosis. SLEDAI-2 K > 5 maintained association with CIMT after adjusting for control variables. Conclusion Subclinical atherosclerosis is frequently observed in cSLE, mainly in patients with moderate to severe disease activity.

scholarly journals A Comparison of the Correlation of Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) with Health-Related Quality of Life

2021 ◽  
Vol 10 (10) ◽  
pp. 2137
Author(s):  
Ning-Sheng Lai ◽  
Ming-Chi Lu ◽  
Hsiu-Hua Chang ◽  
Hui-Chin Lo ◽  
Chia-Wen Hsu ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Information Criterion ◽  
Systemic Lupus Erythematosus Disease ◽  
Systemic Lupus

Background and Aim: The aim of this study was to compare the correlation of a recently developed systemic lupus erythematosus disease activity score (SLE-DAS) with the SLE disease activity index 2000 (SLEDAI-2K) with the Lupus Quality of Life questionnaire (LupusQoL) in Taiwanese patients with SLE. Methods: A cross-sectional study was conducted in a regional teaching hospital in Taiwan from April to August 2019. Adult patients with a clinician-confirmed diagnosis of SLE based on the 1997 American College of Rheumatology revised criteria or the 2012 Systemic Lupus International Collaborating Clinics Classification Criteria were recruited. SLE disease activity was measured with both SLEDAI-2K and SLE-DAS. Disease-specific quality of life was assessed using the LupusQoL. Results: Of the 333 patients with SLE in this study, 90.4% were female and 40% were between the ages of 20 and 39 years. The median SLEDAI-2K score was 4.00 (interquartile range [IQR] 2.00–7.50) and the median SLE-DAS score was 2.08 (IQR 1.12–8.24) in our patients with SLE. After adjusting for sex and age intervals, both SLEDAI-2k and SLE-DAS were significantly and inversely associated with all eight domains of LupusQoL. The magnitudes of the mean absolute error, root mean square error, Akaike Information Criterion, Bayesian Information Criterion, and coefficient of determination were comparable between SLEDAI-2K and SLE-DAS. Conclusions: There were no clear differences in the use of SLE-DAS over SLEDAI-2K in assessing HRQoL in patients with SLE. We suggest that, in this aspect, both SLEDAI-2K and SLE-DAS are effective tools for measuring disease activity in patients with SLE.

Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 Enhances the Ability of SLE Responder Index to Identify Responders in Clinical Trials

2011 ◽  
Vol 38 (11) ◽  
pp. 2395-2399 ◽  
Author(s):  
ZAHI TOUMA ◽  
DAFNA D. GLADMAN ◽  
DOMINIQUE IBAÑEZ ◽  
SHAHRZAD TAGHAVI-ZADEH ◽  
MURRAY B. UROWITZ
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Systemic Lupus ◽  
Original Definition ◽  
Definition Of

Objective.To evaluate the performance of the Systemic Lupus Erythematosus (SLE) Responder Index (SRI) when the SLE Disease Activity Index 2000 (SLEDAI-2K) is substituted with SLEDAI-2K Responder Index-50 (SRI-50), a valid and reliable index of disease activity improvement. Also, to determine whether the SRI-50 will enhance the ability of SRI in detecting responders.Methods.Our study was conducted on patients who attended the Lupus Clinic from September 2009 to September 2010. SLEDAI-2K, SRI-50, the British Isles Lupus Assessment Group measure, and the Physician’s Global Assessment were determined initially and at followup. SRI was determined at the followup visit according to its original definition using the SLEDAI-2K score and by substituting SLEDAI-2K with SRI-50.Results.A total of 117 patients with SLEDAI-2K ≥ 4 at baseline were studied. Patients had 1 followup visit over a 3-month period. Twenty-nine percent of patients met the original definition of SRI and 35% of patients met the definition of SRI when SLEDAI-2K was substituted with SRI-50. The use of SRI-50 allowed determination of significant improvement in 7 additional patients. This improvement could not be discerned with the use of SLEDAI-2K as a component of SRI. At followup visits that showed improvement, SRI-50 scores decreased to a greater extent than SLEDAI-2K scores (p < 0.0001).Conclusion.SRI-50 enhances the ability of SRI to identify patients with clinically important improvement in disease activity. SRI-50 was superior to SLEDAI-2K in detecting partial clinical improvement, ≥ 50%, between visits. These properties of the SRI-50 enable it to be used as an independent outcome measure of improvement or as a component of SRI in clinical trials.

Optimal Frequency of Visits for Patients with Systemic Lupus Erythematosus to Measure Disease Activity Over Time

2010 ◽  
Vol 38 (1) ◽  
pp. 60-63 ◽  
Author(s):  
DOMINIQUE IBAÑEZ ◽  
DAFNA D. GLADMAN ◽  
ZAHI TOUMA ◽  
MANDANA NIKPOUR ◽  
MURRAY B. UROWITZ
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Systemic Lupus ◽  
The Mean ◽  
Over Time ◽  
Measure Disease Activity ◽  
Lupus Disease Activity

Objective.Adjusted mean Systemic Lupus Erythematosus Disease Activity Index (SLEDAI; AMS) measures lupus disease activity over time. Our aim was to determine optimal visit frequency for calculating AMS.Methods.Patients followed monthly for 12 consecutive visits were included. AMS was calculated using all of the SLEDAI 2000 (AMSGOLD using all 12 visits), only quarterly visits (AMS3, using visits 3 months apart), semiannual visits (AMS6, using first, middle, and last visits only), and annual visits (AMS12, using only the first and last visits). Comparisons of AMS3, AMS6, and AMS12 with AMSGOLD are made using descriptive statistics.Results.Seventy-eight patients were included (92% women, mean age at SLE diagnosis 30.1 yrs and at study start 46.2 yrs). The mean (SD) AMSGOLD for the entire year was 2.05 (1.66), for AMS3 1.99 (1.65), for AMS6 2.12 (1.87), and for AMS12 2.08 (1.83). Mean (SD) of the absolute differences with AMSGOLD: for AMS3 0.29 (0.33), for AMS6 0.45 (0.59), and for AMS12 0.61 (0.58). Differences that were < 0.5 were considered minimal while those ≥ 1 were deemed important. Comparing AMSGOLD to AMS3, 82% of the differences were minimal and 3% were important. When comparing to AMS6, 68% were minimal and 10% were important, while comparing to AMS12, 50% were minimal and 21% were important.Conclusion.Usual clinic visits occurring quarterly offer a good estimation of disease activity over a 1-year period and are preferred over semiannual and annual visits.

Serum Albumin as a Marker for Disease Activity in Patients with Systemic Lupus Erythematosus

2010 ◽  
Vol 37 (8) ◽  
pp. 1667-1672 ◽  
Author(s):  
JONATHAN YIP ◽  
ELAHEH AGHDASSI ◽  
JIANDONG SU ◽  
WENDY LOU ◽  
HEATHER REICH ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Serum Albumin ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Mixed Model ◽  
Activity Index ◽  
Surrogate Marker ◽  
Disease Activity Index ◽  
Systemic Lupus ◽  
University Of Toronto

Objective.To determine whether serum albumin reflects disease activity in patients with systemic lupus erythematosus (SLE) with and without nephritis (LN, LNN), and whether serum albumin could be a surrogate marker of SLE disease activity overall. There is currently no clinical “gold standard” in the assessment of disease activity in SLE.Methods.Patients with ≥ 3 clinic visits within a maximum followup period of 10 years were selected from the University of Toronto Lupus Clinic database. Subjects were divided into 3 groups: LN-B, those with nephritis defined by histological findings on renal biopsies; LN-L, those with nephritis defined by laboratory abnormalities in the absence of biopsy; and LNN, those without nephritis. In a subanalysis, the renal groups were further stratified by proteinuria status. The associations of SLE-Disease Activity Index (SLEDAI-2K) with serum albumin and dsDNA were examined using the mixed model regression analysis.Results.A total of 1078 patients were studied: 89.1% female, 71.5% white, mean age 33.6 (SD 12.6) years, and with median baseline SLEDAI-2K of 8. Serum albumin was more significantly associated with SLEDAI in LN-B and LN-L. The association was also present but weaker in the LNN group. In all LN, the associations between serum albumin and SLEDAI-2K were stronger in those with proteinuria.Conclusion.In patients with SLE, higher SLEDAI was associated with lower serum albumin levels.

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.

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