scholarly journals Dendritic cells’ characteristics in patients with treated systemic lupus erythematosus

2020 ◽  
Author(s):  
Anna Wardowska ◽  
Żaneta Smoleńska ◽  
Katarzyna A. Lisowska ◽  
Zbigniew Zdrojewski ◽  
Michał Pikuła
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dendritic Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Complement Components ◽  
Expression Of Genes ◽  
Luminex Technology ◽  
Transcriptional Changes ◽  
Chronic Autoimmune Disease

The systemic lupus erythematosus (SLE) is a chronic autoimmune disease related to a loss of immune tolerance against autoantigens that leads to tissue inflammation and organ dysfunction. Constant stimulation of dendritic cells (DC) with autoantigens is hypothesized to increase the B cells’ activity which are involved in production of autoantibodies that play an essential role in the SLE development. We focused our study on detecting alterations in DCs at the cellular and molecular levels in patients with treated SLE, depending on the disease activity and treatment. In order to phenotype subpopulations of DCs, multicolor flow cytometry was used. Transcriptional changes were identified with quantitative PCR, while soluble cytokine receptors were assessed with the Luminex technology. We show that SLE patients display a higher percentage of activated myeloid DCs (mDCs) when compared to healthy people. Both, the mDCs and plasmacytoid DCs (pDCs) of SLE patients were characterized by changes in expression of genes associated with their maturation, functioning and signalling, which was especially reflected by low expression of regulatory factor ID2 and increased expression of IRF5. pDCs of SLE patients also showed increased expression of IRF1. There were also significant changes in the expression of APRIL, MBD2, and E2-2 in mDCs that significantly correlated with some serum components, i.e. anti-dsDNA antibodies or complement components. However, we did not find any significant differences depending on the disease activity. While the majority of available studies focuses mainly on the role of pDCs in the disease development, our results show significant disturbances in the functioning of mDCs in SLE patients, thus confirming mDCs’ importance in SLE pathogenesis.

Altered redox regulation by Nrf2-Keap1 system in dendritic cells of systemic lupus erythematosus patients

Lupus ◽  
2020 ◽  
Vol 29 (12) ◽  
pp. 1544-1555
Author(s):  
Preeti Gautam ◽  
Gurjasmine Kaur ◽  
Ankit Tandon ◽  
Aman Sharma ◽  
Archana Bhatnagar
Keyword(s):  
Oxidative Stress ◽  
Systemic Lupus Erythematosus ◽  
Dendritic Cells ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Redox Regulation ◽  
Recent Change ◽  
Type I ◽  
Systemic Lupus ◽  
Type I Ifns

Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with inflammation and multiple organ involvement. Individually, dendritic cells (DCs) and oxidative stress have been well discussed for their critical involvement in the pathogenesis of disease but the precise impact of oxidative stress on DCs in relation to SLE disease activity is yet to be scrutinized. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1) pathway is the cellular mechanism to combat increased reactive oxygen species (ROS). The current study was framed in order to understand redox regulation in DCs along with an argument in context to disease activity. Here, 23 SLE patients along with 10 healthy controls were enrolled and disease activity was calculated as the recent change in SLEDAI score. We found the percentage of circulating plasmacytoid DCs (pDCs) was increased with an increase in disease activity. Altered DCs functionality along with disease activity was further supported with the differential concentration of Type I IFNs. The disease activity was positively associated with increased levels of ROS. A relevant reason for increased ROS was further explained with the decreased levels of transcription factor Nrf2. Hence, the present study suggests that SLE specific DCs displayed elevation in ROS and this outcome might be due to impaired free radical clearance by Nrf2. Correlation studies further established an association of disease activity with increased ROS, Type I IFNs levels and decreased activity of oxidative stress regulating enzymes.

scholarly journals Performance Characteristics of Different Anti-Double-Stranded DNA Antibody Assays in the Monitoring of Systemic Lupus Erythematosus

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Michael Mahler ◽  
Chelsea Bentow ◽  
Tyler O’Malley ◽  
Claudia Ibarra ◽  
John Conklin ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Mixed Effects ◽  
Performance Characteristics ◽  
High Avidity ◽  
Systemic Lupus ◽  
Complement Components ◽  
Linear Mixed Effects ◽  
Double Stranded Dna

Objective. We sought to evaluate different anti-double-stranded DNA assays for their performance characteristics in monitoring disease activity fluctuations in systemic lupus erythematosus (SLE). Methods. 36 active SLE patients were followed monthly. At each study visit (total n=371), blood was collected and disease activity was scored using the SELENA-SLEDAI (excluding anti-dsDNA or complement components) and by a physician’s global assessment (PGA). Four anti-dsDNA tests were compared. Linear mixed-effects models with random intercept and fixed slopes were used to evaluate the relationship between the longitudinal fluctuations of disease activity and anti-dsDNA titers. Results. At enrollment, positivity for QUANTA Lite and high-avidity anti-dsDNA assay was both 64% and significantly lower than anti-dsDNA positivity by QUANTA Flash (83%) and CLIFT (96%). Linear mixed-effects modeling indicated that the change in clinical SELENA-SLEDAI scores was associated with the titers of all anti-dsDNA with QUANTA Flash yielding the highest marginal R2 (0.15; p<0.01). QUANTA Flash was the only anti-dsDNA assay significantly associated with the change in PGA (marginal R2=0.05; p<0.01). Conclusion. These data indicate that anti-dsDNA antibodies determined by QUANTA Flash have a value in monitoring SLE disease activity.

Utility of Interferon-α as a Biomarker in Central Neuropsychiatric Involvement in Systemic Lupus Erythematosus

2012 ◽  
Vol 39 (3) ◽  
pp. 504-509 ◽  
Author(s):  
HILDA FRAGOSO-LOYO ◽  
YEMIL ATISHA-FREGOSO ◽  
CARLOS A. NÚÑEZ-ALVAREZ ◽  
LUIS LLORENTE ◽  
JORGE SÁNCHEZ-GUERRERO
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Disease Activity Index ◽  
Study Groups ◽  
Interferon Α ◽  
Systemic Lupus ◽  
Serum Samples ◽  
Luminex Technology

Objective.To assess the utility of interferon-α (IFN-α) in serum and cerebrospinal fluid (CSF) as a biomarker of disease activity in central neuropsychiatric systemic lupus erythematosus (cNPSLE).Methods.Serum and CSF samples were drawn at hospitalization in 34 patients with cNPSLE, 16 surgical SLE, 4 primary neuropsychiatric conditions, and 25 with nonautoimmune conditions, except in 44 non-NPSLE patients in whom only serum was studied. Six months later, serum/CSF and serum samples were taken in 20 cNPSLE and 35 non-NPSLE patients, respectively. SLE activity was assessed at hospitalization, and 6 months later in cNPSLE and non-NPSLE patients. IFN-α was detected by Luminex technology.Results.The mean ± SD age of patients with cNPSLE was 31.4 ± 12.2 years, which was similar across the study groups (p = 0.46). Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) scores among cNPSLE, non-NPSLE, and SLE-surgical patients were 15.3 ± 8.2, 12.4 ± 8.2, and 3.8 ± 1.5, respectively. IFN-α levels in serum were higher in cNPSLE than in nonautoimmune patients (p = 0.02), but were similar to non-NPSLE and SLE-surgical groups. In CSF samples, IFN-α levels were higher in cNPSLE than in nonautoimmune patients (p = 0.03), and were nonsignificantly higher than in SLE-surgical and primary neuropsychiatric patients. Six months later, serum levels of IFN-α did not vary from baseline values despite a significant decrease in SLEDAI-2K score in cNPSLE and non-NPSLE patients. IFN-α levels in the CSF of patients with cNPSLE also remained stable. Among specific cNPSLE syndromes, CSF IFN-α levels were significantly higher among patients with acute confusional syndrome.Conclusion.IFN-α does not seem to represent a useful biomarker of cNPSLE syndromes; its utility in specific cNPSLE manifestations merits further investigation.

Disease activity-dependent expression of nerve growth factor TRKA and P75 receptors on elevated dendritic cells and peripheral leucocytes in patients with systemic lupus erythematosus

Lupus ◽  
2020 ◽  
Vol 29 (8) ◽  
pp. 970-975 ◽  
Author(s):  
Stefanie Welle ◽  
Anna M Wolf ◽  
Christian Dernbach ◽  
Ute Klarmann-Schulz ◽  
Matthias F Seidel
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Dendritic Cells ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Inflammatory Diseases ◽  
Receptor Expression ◽  
Systemic Lupus ◽  
Nerve Growth

Introduction The nervous system modulates rheumatic diseases in neurogenic inflammation (NI). Nerve growth factor (NGF) plays a pivotal role in NI and chronic nociceptive pain. However, the role of NGF in autoimmune inflammatory diseases is not well understood. The aim of this study was to analyse NGF high- (TrkA) and low-affinity (p75) receptors on all major leucocyte subsets of patients with systemic lupus erythematosus (SLE) as a potential indicator of NI. Methods A total of 13 patients were analysed by fluorescence-activated cell sorting and compared to 13 healthy control (HC) subjects. Patients were also stratified for high or low disease activity (CRP, ESR, SLEDAI, ANA, anti-dsDNA and C3/C4). Statistics included the Kruskal–Wallis test and Mann–Whitney U-test. Results When comparing patients and HC, TrkA was not differentially expressed. In contrast, p75 was increased on CD16+ and CD56+ leucocytes in patients. CD11c+ dendritic cells (DC) were in total increased in SLE. DCs were also significantly elevated in active patients. Furthermore, we found an intermediate CD11b+ population strongly expressing TrkA in patients and HC. Conclusion We demonstrate for the first time differential NGF receptor expression in SLE. The increased CD11c+ DCs might indicate additional activation in SLE.

Sign in / Sign up

Export Citation Format

Share Document