scholarly journals Mechanistic Paradigms of Natural Plant Metabolites as Remedial Candidates for Systemic Lupus Erythromatosus

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 1049
Author(s):  
Acharya Balkrishna ◽  
Pallavi Thakur ◽  
Shivam Singh ◽  
Swami Narsingh Chandra Dev ◽  
Anurag Varshney
Keyword(s):  
Lupus Erythematosus ◽  
Intracellular Signaling ◽  
Drug Targets ◽  
Symptomatic Relief ◽  
Autoimmune Disorder ◽  
Multiple Organ ◽  
Plant Metabolites ◽  
Systemic Lupus ◽  
Disease Heterogeneity ◽  
Natural Plant

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder involving a dysregulated immune response which ultimately leads to multiple organ failure. Several immunological and cellular checkpoints are available as drug targets. However, the available chemosynthetic drugs such as non-steroidal anti-inflammatory drugs and corticosteroids provide limited therapy with extreme toxicities. Moreover, the disease heterogeneity in SLE is very difficult to manage by a single drug component. Hence, it is imperative to utilize the holistic capabilities of natural plant products as immunomodulators and intracellular signaling regulators, thereby providing an auxiliary option of treatment. Additionally, the herbal drugs also serve as symptomatic relief providers, thereby serving as a prophylactic remedy in case of cerebrovascular, hepatic, nephropathological, hematological, cardiopulmonary, mucocutaneous and musculoskeletal manifestations of SLE. The present review attempts to showcase the current state of knowledge regarding the utility of plant-derived phyto-metabolites with their probable mechanistic roles in treating SLE, by means of targeting the signaling cascade, proinflammatory cytokine production and B–T cell co-stimulation. It is hoped that further preclinical and clinical studies will be embarked upon in order to understand the underlying therapeutic and mechanistic aspects of these medicinal herbs.

scholarly journals Immune Profiling and Precision Medicine in Systemic Lupus Erythematosus

Cells ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 140 ◽  
Author(s):  
Yasuo Nagafuchi ◽  
Hirofumi Shoda ◽  
Keishi Fujio
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Precision Medicine ◽  
Lupus Erythematosus ◽  
Clinical Symptoms ◽  
Autoimmune Disorder ◽  
Molecular Networks ◽  
Systemic Lupus ◽  
Disease Heterogeneity ◽  
Wide Range ◽  
Immune Profiling

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a wide range of clinical symptoms. Enormous progress has been made in the immunological and genetic understanding of SLE. However, the biology of disease heterogeneity in SLE has remained largely unexplored. Human immune profiling studies, helped by recent technological advances especially in single-cell and “omics” analyses, are now shedding light on the cellular and molecular basis of clinical symptoms and disease flares in individual patients. Peripheral blood immunophenotyping analysis with flow cytometry or mass cytometry are identifying responsible cell subsets and markers characteristic of disease heterogeneity. Transcriptome analysis is discovering molecular networks responsible for disease activity, disease subtype and future relapse. In this review, we summarize recent advances in the immune profiling analysis of SLE patients and discuss how they will be used for future precision medicine.

scholarly journals LUPUS

2008 ◽  
Vol 15 (01) ◽  
pp. 179-184
Author(s):  
NAGEEN HUSSAIN
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Immune System ◽  
Lupus Erythematosus ◽  
Immune Complexes ◽  
Autoimmune Disorder ◽  
Multiple Organ ◽  
The Self ◽  
Systemic Lupus ◽  
Organ Systems ◽  
Self Antigens

Lupus is an autoimmune disorder in which the immune system becomeshyperactive; results in the formation of auto-antibodies that react with the “self” antigens to form immune complexes.These immune complexes build up in the tissues; can cause inflammation, injury to tissues, pain and bring about thesymptoms . Systemic Lupus Erythematosus (SLE) is one of the type of lupus which affects multiple organ systems 1,2and is multifactorial in etiology .2,3

scholarly journals Characterization of the thrombin generation profile in systemic lupus erythematosus

2017 ◽  
Vol 104 (1) ◽  
pp. 35-41 ◽  
Author(s):  
A Kern ◽  
E Barabás ◽  
A Balog ◽  
Sz Burcsár ◽  
M Kiszelák ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Thrombin Generation ◽  
Area Under The Curve ◽  
Autoimmune Disorder ◽  
Systemic Lupus ◽  
Time To Peak ◽  
Cat Assay ◽  
Coagulation Tests ◽  
Healthy Control

Systemic lupus erythematosus (SLE) is a multisystemic inflammatory autoimmune disorder. Thrombotic events occur at a higher incidence among SLE patients. The investigation of thrombin generation (TG) with calibrated automated thrombogram (CAT) test as a global hemostasis assay is applicable for the overall functional assessment of the hemostasis. The aim of this study was to characterize the hemostatic alterations observed in SLE by CAT assay. In this study, CAT parameters and basic coagulation parameters of SLE patients (n = 22) and healthy control subjects (n = 34) were compared. CAT area under the curve (i.e., endogenous thrombin potential) was lower than normal in SLE (807 vs. 1,159 nM*min, respectively), whereas other CAT parameters (peak, lag time, time to peak, and velocity index) and the basic coagulation tests were within the normal range. The presence of anti-phospholipid antibodies and the applied therapy was not associated with hemostasis parameters in SLE. We concluded that the reported high risk of thrombosis is not related to TG potential.

scholarly journals MiR-410 Down-Regulates the Expression of Interleukin-10 by Targeting STAT3 in the Pathogenesis of Systemic Lupus Erythematosus

2016 ◽  
Vol 39 (1) ◽  
pp. 303-315 ◽  
Author(s):  
Dongmei Liu ◽  
Na Zhang ◽  
Xiaomei Zhang ◽  
Muting Qin ◽  
Youdan Dong ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Lupus Erythematosus ◽  
Autoimmune Disorder ◽  
Interleukin 10 ◽  
Luciferase Assay ◽  
Mrna Levels ◽  
Healthy Controls ◽  
Systemic Lupus ◽  
Targeting Effect

Background/Aims: Systemic lupus erythematosus (SLE) is a heterogeneous chronic inflammatory autoimmune disorder, in the pathogenesis of which miRNAs play a versatile function. The purpose of this study was to investigate the effect of miRNA-410 on the pathogenesis of SLE in T cells of SLE patients. Methods: Real-time PCR was used to test the mRNA levels of miRNA-410 in SLE patients and healthy controls. ELISA analysis was performed to examine the production levels of IL-10. Luciferase Assay was used to confirm the targeting effect of miRNA-410 on 3'UTR of STAT3 mRNA. Results: We found that the expression level of miR-410 in T cells of SLE patients was decreased comparing to that in healthy controls, whereas overexpression of miR-410 significantly reduced the expression levels of IL-10. Furthermore, miR-410 suppresses the transcription activity of STAT3 by binding directly to the 3 'UTR of STAT3 mRNA. Moreover, silence of STAT3 down regulated IL-10 expression in CD3+ T cells. Conclusion: Our results demonstrate that miR-410 is the key regulatory factor in the pathogenesis of SLE by regulating the expression of IL-10 through targeting STAT3. These data suggest a novel function of miR-410 and bring new insight into understanding the complex mechanisms involved in SLE.

scholarly journals A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus Erythematosus: Diagnostic Utility of ADAMTS-13 Activity

2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Risa Yamada ◽  
Kazuhisa Nozawa ◽  
Takashi Yoshimine ◽  
Yoshinari Takasaki ◽  
Hideoki Ogawa ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Thrombotic Microangiopathy ◽  
Autoimmune Disorder ◽  
Accurate Diagnosis ◽  
Diagnostic Utility ◽  
Systemic Lupus

Thrombotic thrombocytopenia purpura (TTP) caused by a deficiency in ADAMTS-13 activity is considered to involve a subset of thrombotic microangiopathy (TMA). Although concept of TTP is included under the umbrella of TMA, discrimination of TTP from TMA is occasionally difficult in an autoimmune disorder. Herein, we report a case with TTP associated with systemic lupus erythematosus (SLE). In this case, it was difficult to discriminate TTP from TMA and the measurement of ADAMTS-13 activity was useful for obtaining an accurate diagnosis. SLE patients having thrombocytopenia in complication with anemia should be considered a monitoring of ADAMTS-13 activity even though the patients lacked symptoms of TTP related to the microvascular coagulation.

scholarly journals Machine learning applied to whole-blood RNA-sequencing data uncovers distinct subsets of patients with systemic lupus erythematosus

2019 ◽  
Author(s):  
William A Figgett ◽  
Katherine Monaghan ◽  
Milica Ng ◽  
Monther Alhamdoosh ◽  
Eugene Maraskovsky ◽  
...  
Keyword(s):  
Gene Expression ◽  
Machine Learning ◽  
Systemic Lupus Erythematosus ◽  
Clinical Trials ◽  
Lupus Erythematosus ◽  
Whole Blood ◽  
Rna Seq ◽  
Systemic Lupus ◽  
Disease Heterogeneity ◽  
Healthy Donors

ABSTRACTObjectiveSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease that is difficult to treat. There is currently no optimal stratification of patients with SLE, and thus responses to available treatments are unpredictable. Here, we developed a new stratification scheme for patients with SLE, based on the whole-blood transcriptomes of patients with SLE.MethodsWe applied machine learning approaches to RNA-sequencing (RNA-seq) datasets to stratify patients with SLE into four distinct clusters based on their gene expression profiles. A meta-analysis on two recently published whole-blood RNA-seq datasets was carried out and an additional similar dataset of 30 patients with SLE and 29 healthy donors was contributed in this research; 141 patients with SLE and 51 healthy donors were analysed in total.ResultsExamination of SLE clusters, as opposed to unstratified SLE patients, revealed underappreciated differences in the pattern of expression of disease-related genes relative to clinical presentation. Moreover, gene signatures correlated to flare activity were successfully identified.ConclusionGiven that disease heterogeneity has confounded research studies and clinical trials, our approach addresses current unmet medical needs and provides a greater understanding of SLE heterogeneity in humans. Stratification of patients based on gene expression signatures may be a valuable strategy to harness disease heterogeneity and identify patient populations that may be at an increased risk of disease symptoms. Further, this approach can be used to understand the variability in responsiveness to therapeutics, thereby improving the design of clinical trials and advancing personalised therapy.

Autoantibody profiling reveals four protein candidate autoantigens associated with systemic lupus erythematosus

Lupus ◽  
2018 ◽  
Vol 27 (10) ◽  
pp. 1670-1678 ◽  
Author(s):  
J Frostegård ◽  
C Hellström ◽  
P Nilsson ◽  
A G Frostegård ◽  
S Ajeganova
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Zinc Finger Protein ◽  
Tumor Necrosis Factor Receptor ◽  
Major Complication ◽  
Intima Media Thickness ◽  
Carotid Intima Media Thickness ◽  
Systemic Lupus ◽  
Serum Samples ◽  
Disease Heterogeneity

Objectives In systemic lupus erythematosus (SLE) there are typically many autoantibodies. The disease heterogeneity could be better understood with discovery of phenotype-specific antigens targeted by autoantibodies. We here aimed to identify novel autoantigens potentially related to SLE disease and a major complication, atherosclerosis. Methods Antigen microarrays were used to profile IgG autoantibody reactivity against 77 protein fragments (20–140 amino acids (aa) long, median 89 aa) produced within the Human Protein Atlas project, in serum samples from SLE patients ( n = 107) and age- and sex-matched population-based controls ( n = 107). Common carotid intima-media thickness, plaque occurrence and echogenicity were determined by B-mode ultrasound. Results We determined significant differences between patients and controls in IgG reactivity against four proteins. In patients compared to controls, there was an increase of IgG reactivity against zinc finger protein 688 (ZNF688), early B cell factor 2 (EBF2), crystallin, alpha B (CRYAB) and tumor necrosis factor receptor superfamily member 13C (TNFRSF13C). Of these four antigens, only anti-ZNF688 was associated with carotid atherosclerosis (plaque occurrence) and vulnerable plaques in SLE. There was a weak association between anti-EBF2 and SLE disease activity but no significant associations were determined for other measured IgG reactivity. Conclusions In this discovery screening we here demonstrate new candidate autoantigens with differential reactivity (reflecting autoantibody levels) in SLE patients and in controls and in relation to atherosclerosis in SLE.

Lupus Eritematosus Sistemik pada Pria

2021 ◽  
Vol 3 (2) ◽  
pp. 37-42
Author(s):  
Harry Andrean ◽  
Raveinal Raveinal
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Clinical Course ◽  
Multiple Organ ◽  
Systemic Lupus ◽  
Malar Rash ◽  
Mouth Ulcer ◽  
Pulse Dose ◽  
Aggressive Clinical Course ◽  
Complex Autoimmune Disease

Introduction: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by presence of nucleus autoantibody and affected multiple organ. Systemic lupus erythematosus is more common in women than men with ratio 2:1 to 15:1. Men with SLE often have a more aggressive clinical course, lead to a poorer prognosis compared with women with SLE. Case Report: A man, 29 years old came to hospital with main complain joint pain increased since 1 week ago, accompanied with red spot on face, trunk, hands, foot, and back, hair loss, swollen leg, mouth ulcer, and fatique. Malar rash and discoid rash were identified from physical examination. From laboratorium, ANA profile was positive for RNP/Sm, Sm, dsDNA, and histone. Skin biopsy showed a lupus discoid. Conclusion: The patient was treated with pulse-dose methylprednisolone for 3 days and showed a good response clinically.

An update on diet and nutritional factors in systemic lupus erythematosus management

2017 ◽  
Vol 30 (1) ◽  
pp. 118-137 ◽  
Author(s):  
Marina Aparicio-Soto ◽  
Marina Sánchez-Hidalgo ◽  
Catalina Alarcón-de-la-Lastra
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Diet Therapy ◽  
Multiple Organ ◽  
Dietary Factors ◽  
Clinical Experiences ◽  
Systemic Lupus ◽  
Nutritional Factors ◽  
Biological Heterogeneity

AbstractSystemic lupus erythematosus (SLE) is a chronic inflammatory and autoimmune disease characterised by multiple organ involvement and a large number of complications. SLE management remains complicated owing to the biological heterogeneity between patients and the lack of safe and specific targeted therapies. There is evidence that dietary factors can contribute to the geoepidemiology of autoimmune diseases such as SLE. Thus, diet therapy could be a promising approach in SLE owing to both its potential prophylactic effects, without the side effects of classical pharmacology, and its contribution to reducing co-morbidities and improving quality of life in patients with SLE. However, the question arises as to whether nutrients could ameliorate or exacerbate SLE and how they could modulate inflammation and immune function at a molecular level. The present review summarises preclinical and clinical experiences to provide the reader with an update of the positive and negative aspects of macro- and micronutrients and other nutritional factors, including dietary phenols, on SLE, focusing on the mechanisms of action involved.

scholarly journals Expansion of regulatory T cells using low-dose interleukin-2 attenuates hypertension in an experimental model of systemic lupus erythematosus

2019 ◽  
Vol 317 (5) ◽  
pp. F1274-F1284 ◽  
Author(s):  
Erin B. Taylor ◽  
Jennifer M. Sasser ◽  
Kenji J. Maeda ◽  
Michael J. Ryan
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Lupus Erythematosus ◽  
Renal Injury ◽  
Low Dose ◽  
Interleukin 2 ◽  
Autoimmune Disorder ◽  
Systemic Lupus ◽  
And Control

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder that is characterized by prevalent hypertension, renal injury, and cardiovascular disease. Numerous studies have reported a low prevalence and/or impaired function of regulatory T (TREG) cells in both patients with SLE and murine models of the disease. Evidence suggests that TREG cell dysfunction in SLE results from a deficiency in IL-2. Recent studies have reported that low-dose IL-2 therapy expands TREG cells in mouse models of SLE, but whether expanding TREG cells protects against hypertension and renal injury during SLE is unclear. To examine this question, female SLE (NZBWF1) and control (NZW) mice were injected with vehicle or recombinant mouse IL-2 three times in 24 h followed by single maintenance doses every 5 days for 4 wk. Treatment with IL-2 effectively expanded TREG cell populations in the peripheral blood, spleen, and kidneys. Circulating levels of anti-dsDNA IgG autoantibodies, a marker of SLE disease activity, were higher in SLE mice compared with control mice but were unaffected by IL-2 treatment. As previously reported by our laboratory, mean arterial pressure, measured in conscious mice by a carotid catheter, was higher in SLE mice than in control mice. Mean arterial pressure was significantly lower in IL-2-treated SLE mice compared with vehicle-treated SLE mice, suggesting that expanding TREG cells using low-dose IL-2 attenuates the development of hypertension. While the mechanism for the protection against hypertension is unclear, it does not appear to be related to the delay of SLE disease progression.

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