Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.7
3.4
Journals
Metabolites
Special Issues
Identifying Novel Potential Therapeutic Targets for Treating Lupus by Metabolic...
share announcement

Identifying Novel Potential Therapeutic Targets for Treating Lupus by Metabolic Approaches

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Endocrinology and Clinical Metabolic Research".

Deadline for manuscript submissions: closed (15 November 2021) | Viewed by 18005

Special Issue Editor

Dr. Tamara K. Nowling

E-Mail Website
Guest Editor
Department of Medicine, Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA
Interests: biomarkers; lupus nephritis; glycosphingolipid metabolism; renal cell function; T cell dysfunction

Special Issue Information

Dear Colleagues, 

Systemic lupus erythematosus or lupus is a widely variable and complex disease. Nephritis, a detrimental complication for many lupus patients, is especially difficult to treat, and biomarkers of therapeutic response are lacking, resulting in high morbidity and mortality. While genomics and proteomics have identified dysregulated or dysfunctional molecules and pathways that may serve as potential biomarkers or therapeutic targets in lupus, relatively few studies have focused on metabolomics. Metabolites provide a functional readout of pathophysiological changes in specific tissues. They can also play important roles in modulating immune cells. Thus, the identification of metabolites altered in lupus may be highly advantageous and quickly combined with clinical studies.

This Special Issue of Metabolites will include research articles or reviews investigating the metabolomic changes in lupus. The topics will include, but not be limited to, the identification of lipid, carbohydrate, or amino acid metabolites as potential biomarkers of disease; biomarkers of drug response; and therapeutic targets. Articles describing the mechanisms or roles of metabolites for understanding cellular dysfunction, tissue responses and damage, or disease progression will also be considered. Manuscripts focused on lupus nephritis are highly desired.

Dr. Tamara K. Nowling
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • systemic lupus erythematosus
  • lupus nephritis
  • biomarker
  • therapeutic target
  • therapeutic response
  • drug response
  • metabolomics
  • metabolome
  • lipidomics
  • glycomics

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (6 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

18 pages, 3257 KiB  
Article
Lipidomics Revealed Aberrant Lipid Metabolism Caused by Inflammation in Cardiac Tissue in the Early Stage of Systemic Lupus Erythematosus in a Murine Model
by Jida Zhang, Lu Lu, Xiaoyu Tian, Kaili Wang, Guanqun Xie, Haichang Li, Chengping Wen and Changfeng Hu
Metabolites 2022, 12(5), 415; https://doi.org/10.3390/metabo12050415 - 5 May 2022
Cited by 6 | Viewed by 1923
Abstract
Cardiac involvement, displayed as premature cardiovascular disease (CVD), is one of common clinical symptoms of patients with systemic lupus erythematosus (SLE), contributing to mortality of the disease. The precise underlying pathological mechanism(s) for the cardiac involvement in lupus remains poorly understood. Lipids and [...] Read more.
Cardiac involvement, displayed as premature cardiovascular disease (CVD), is one of common clinical symptoms of patients with systemic lupus erythematosus (SLE), contributing to mortality of the disease. The precise underlying pathological mechanism(s) for the cardiac involvement in lupus remains poorly understood. Lipids and their metabolites are directly involved in atherosclerosis development, oxidative stress, and inflammation, which are closely related to the development of CVD. In the study, shotgun lipidomics was exploited to quantitatively analyze cellular lipidomes in the cardiac tissue of MRL/lpr mice at two different time points (i.e., pre-lupus and lupus state) with/without treatment with glucocorticoids (GCs). Urine protein, spleen index, and renal histopathological evaluation of the mice were also performed for assessment of SLE onset and/or outcome. Lipidomics analysis revealed that the deposition of cholesterol and the aberrant metabolism of lipids caused by the increased energy metabolism and the enhanced activation of phospholipases, both of which were originally induced by inflammation, were already present in cardiac tissues from lupus-prone mice even at pre-lupus state. These lipid alterations could further induce inflammation and autoimmune responses, accelerating the process of CVD. In addition, the present study also demonstrated that GCs therapy could not only delay the progression of SLE, but also partially corrected these alterations of lipid species in cardiac tissue due to their anti-inflammatory effect. Thus, the medications with better anti-inflammatory effect might be a useful therapeutic method for premature CVD of SLE. Full article
(This article belongs to the Special Issue Identifying Novel Potential Therapeutic Targets for Treating Lupus by Metabolic Approaches)
►▼ Show Figures

Figure 1

13 pages, 1318 KiB  
Article
Glycosphingolipid Levels in Urine Extracellular Vesicles Enhance Prediction of Therapeutic Response in Lupus Nephritis
by Brian Troyer, Jessalyn Rodgers, Bethany J. Wolf, James C. Oates, Richard R. Drake and Tamara K. Nowling
Metabolites 2022, 12(2), 134; https://doi.org/10.3390/metabo12020134 - 1 Feb 2022
Cited by 5 | Viewed by 1783
Abstract
The development of nephritis increases the risk of morbidity and mortality in systemic lupus erythematosus (SLE) patients. While standard induction therapies, such as mycophenolate mofetil (MMF) induce clinical remission (i.e., complete response) in approximately 50% of SLE patients with nephritis, many patients fail [...] Read more.
The development of nephritis increases the risk of morbidity and mortality in systemic lupus erythematosus (SLE) patients. While standard induction therapies, such as mycophenolate mofetil (MMF) induce clinical remission (i.e., complete response) in approximately 50% of SLE patients with nephritis, many patients fail to respond. Therapeutic response is often not assessed until 6–12 months after beginning treatment. Those patients that fail to respond to treatment continue to accumulate organ damage, thus, there is a critical need to predict which patients will fail therapy before beginning treatment, allowing physicians to optimize therapy. Our previous studies demonstrated elevated urine, but not serum, glycosphingolipids (GSLs) in SLE patients with nephritis compared to SLE patients without nephritis, suggesting the urine GSLs were derived from the kidney. In this study, we measured the GSLs hexosylceramide and lactosylceramide in extracellular vesicles isolated from longitudinal urine samples of LN patients that were treated with MMF for 12 months. GSL levels were significantly elevated in the baseline samples (prior to treatment) of non-responders compared to complete responders. While a few other proteins measured in the whole urine were higher in non-responders at baseline, only GSLs demonstrated a significant ability to discriminate treatment response in lupus nephritis patients. Full article
(This article belongs to the Special Issue Identifying Novel Potential Therapeutic Targets for Treating Lupus by Metabolic Approaches)
►▼ Show Figures

Graphical abstract

20 pages, 3198 KiB  
Article
Metabolomics Defines Complex Patterns of Dyslipidaemia in Juvenile-SLE Patients Associated with Inflammation and Potential Cardiovascular Disease Risk
by George A. Robinson, Junjie Peng, Ines Pineda-Torra, Coziana Ciurtin and Elizabeth C. Jury
Metabolites 2022, 12(1), 3; https://doi.org/10.3390/metabo12010003 - 21 Dec 2021
Cited by 17 | Viewed by 3988
Abstract
Cardiovascular disease (CVD) is a leading cause of mortality in patients with juvenile-onset systemic lupus erythematosus (JSLE) associated with atherosclerosis. The interplay between dyslipidaemia and inflammation—mechanisms that drive atherosclerosis—were investigated retrospectively in adolescent JSLE patients using lipoprotein-based serum metabolomics in patients with active [...] Read more.
Cardiovascular disease (CVD) is a leading cause of mortality in patients with juvenile-onset systemic lupus erythematosus (JSLE) associated with atherosclerosis. The interplay between dyslipidaemia and inflammation—mechanisms that drive atherosclerosis—were investigated retrospectively in adolescent JSLE patients using lipoprotein-based serum metabolomics in patients with active and inactive disease, compared to healthy controls (HCs). Data was analysed using machine learning, logistic regression, and linear regression. Dyslipidaemia in JSLE patients was characterised by lower levels of small atheroprotective high-density lipoprotein subsets compared to HCs. These changes were exacerbated by active disease and additionally associated with significantly higher atherogenic very-low-density lipoproteins (VLDL) compared to patients with low disease activity. Atherogenic lipoprotein subset expression correlated positively with clinical and serological markers of JSLE disease activity/inflammation and was associated with disturbed liver function, and elevated expression of T-cell and B-cell lipid rafts (cell signalling platforms mediating immune cell activation). Finally, exposing VLDL/LDL from patients with active disease to HC lymphocytes induced a significant increase in lymphocyte lipid raft activation compared to VLDL/LDL from inactive patients. Thus, metabolomic analysis identified complex patterns of atherogenic dyslipidaemia in JSLE patients associated with inflammation. This could inform lipid-targeted therapies in JSLE to improve cardiovascular outcomes. Full article
(This article belongs to the Special Issue Identifying Novel Potential Therapeutic Targets for Treating Lupus by Metabolic Approaches)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

13 pages, 298 KiB  
Review
Antibodies against Phosphorylcholine—Implications for Chronic Inflammatory Diseases
by Johan Frostegård
Metabolites 2023, 13(6), 720; https://doi.org/10.3390/metabo13060720 - 1 Jun 2023
Cited by 1 | Viewed by 1763
Abstract
Atherosclerosis and its main consequence, cardiovascular disease (CVD) are nowadays regarded as chronic inflammatory disease conditions, and CVD is the main cause of death in the world. Other examples of chronic inflammation are rheumatic and other autoimmune conditions, but also diabetes, obesity, and [...] Read more.
Atherosclerosis and its main consequence, cardiovascular disease (CVD) are nowadays regarded as chronic inflammatory disease conditions, and CVD is the main cause of death in the world. Other examples of chronic inflammation are rheumatic and other autoimmune conditions, but also diabetes, obesity, and even osteoarthritis among others. In addition, infectious diseases can have traits in common with these conditions. Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease, where atherosclerosis is increased and the risk of CVD is very high. This is a clinical problem but could also shed light on the role of the immune system in atherosclerosis and CVD. Underlying mechanisms are of major interest and these are only partially known. Phosphorylcholine (PC) is a small lipid-related antigen, which is both a danger associated molecular pattern (DAMP), and a pathogen associated molecular pattern (PAMP). Antibodies against PC are ubiquitous and 5–10% of circulating IgM is IgM anti-PC. Anti-PC, especially IgM and IgG1 anti-PC, has been associated with protection in the chronic inflammatory conditions mentioned above, and develops during the first years of life, while being present at very low levels at birth. Animal experiments with immunization to raise anti-PC ameliorate atherosclerosis and other chronic inflammatory conditions. Potential mechanisms include anti-inflammatory, immune modulatory, clearance of dead cells and protection against infectious agents. An intriguing possibility is to raise anti-PC levels through immunization, to prevent and/or ameliorate chronic inflammation. Full article
(This article belongs to the Special Issue Identifying Novel Potential Therapeutic Targets for Treating Lupus by Metabolic Approaches)
►▼ Show Figures

Graphical abstract

22 pages, 1449 KiB  
Review
The Potential of Nrf2 Activation as a Therapeutic Target in Systemic Lupus Erythematosus
by Michelle T. Barati and Dawn J. Caster
Metabolites 2022, 12(2), 151; https://doi.org/10.3390/metabo12020151 - 6 Feb 2022
Cited by 12 | Viewed by 3223
Abstract
Inflammation and oxidative stress are well established in systemic lupus erythematosus (SLE) and are critical to the pathogenesis of autoimmune diseases. The transcription factor NF-E2 related factor 2 (Nrf2) is a central regulator of cellular anti-oxidative responses, inflammation, and restoration of redox balance. [...] Read more.
Inflammation and oxidative stress are well established in systemic lupus erythematosus (SLE) and are critical to the pathogenesis of autoimmune diseases. The transcription factor NF-E2 related factor 2 (Nrf2) is a central regulator of cellular anti-oxidative responses, inflammation, and restoration of redox balance. Accumulating reports support an emerging role for the regulation of Nrf2 in SLE. These include findings on the development of lupus-like autoimmune nephritis and altered immune cell populations in mice lacking Nrf2, as well as decreased Nrf2 abundance in the dendritic cells of patients with SLE. Nrf2-inducing agents have been shown to alleviate oxidative and inflammatory stress and reduce tissue injury in SLE mouse models. Since Nrf2 expression can be increased in activated T cells, the precise role of Nrf2 activation in different immune cell types and their function remains to be defined. However, targeting Nrf2 for the treatment of diseases associated with oxidative stress and inflammation, such as SLE, is promising. As investigation of Nrf2-inducing agents in clinical trials grows, defining the signaling and molecular mechanisms of action and downstream effects in response to different Nrf2-inducing agents in specific cells, tissues, and diseases, will be critical for effective clinical use. Full article
(This article belongs to the Special Issue Identifying Novel Potential Therapeutic Targets for Treating Lupus by Metabolic Approaches)
►▼ Show Figures

Figure 1

16 pages, 1122 KiB  
Review
Altered Germinal-Center Metabolism in B Cells in Autoimmunity
by Ashton K. Shiraz, Eric J. Panther and Christopher M. Reilly
Metabolites 2022, 12(1), 40; https://doi.org/10.3390/metabo12010040 - 5 Jan 2022
Cited by 6 | Viewed by 4353
Abstract
B lymphocytes play an important role in the pathophysiology of many autoimmune disorders by producing autoantibodies, secreting cytokines, and presenting antigens. B cells undergo extreme physiological changes as they develop and differentiate. Aberrant function in tolerogenic checkpoints and the metabolic state of B [...] Read more.
B lymphocytes play an important role in the pathophysiology of many autoimmune disorders by producing autoantibodies, secreting cytokines, and presenting antigens. B cells undergo extreme physiological changes as they develop and differentiate. Aberrant function in tolerogenic checkpoints and the metabolic state of B cells might be the contributing factors to the dysfunctionality of autoimmune B cells. Understanding B-cell metabolism in autoimmunity is important as it can give rise to new treatments. Recent investigations have revealed that alterations in metabolism occur in the activation of B cells. Several reports have suggested that germinal center (GC) B cells of individuals with systemic lupus erythematosus (SLE) have altered metabolic function. GCs are unique microenvironments in which the delicate and complex process of B-cell affinity maturation occurs through somatic hypermutation (SHM) and class switching recombination (CSR) and where Bcl6 tightly regulates B-cell differentiation into memory B-cells or plasma cells. GC B cells rely heavily on glucose, fatty acids, and oxidative phosphorylation (OXPHOS) for their energy requirements. However, the complicated association between GC B cells and their metabolism is still not clearly understood. Here, we review several studies of B-cell metabolism, highlighting the significant transformations that occur in GC progression, and suggest possible approaches that may be investigated to more precisely target aberrant B-cell metabolism in SLE. Full article
(This article belongs to the Special Issue Identifying Novel Potential Therapeutic Targets for Treating Lupus by Metabolic Approaches)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-6
Back to TopTop