Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.4
3.9
Journals
JCM
Special Issues
New Insights into Systemic Lupus Erythematosus: From Immunopathogenesis to Treatment...
share announcement

New Insights into Systemic Lupus Erythematosus: From Immunopathogenesis to Treatment Strategies

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Immunology".

Deadline for manuscript submissions: closed (30 July 2019) | Viewed by 38583

Special Issue Editor

Dr. Carmelo Carmona-Rivera

E-Mail Website
Guest Editor
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), Bethesda, MD, USA
Interests: neutrophils; post-translational modifications; innate immunity; NETs; autoinflammation; hidradenitis suppurativa; rheumatoid arthritis

Special Issue Information

Dear Colleagues,

Systemic Lupus Erytematosus (SLE) is an autoimmune disorder characterized by profound dysregulation of the innate and adaptive immune responses with the aberrant production of proinflammatory cytokines, generation of antinuclear antibodies and multiorgan damage. SLE patients are also at a significant risk of cardiovascular complications such as accelearated atherosclerosis largely driven by immune alterartions. Therefore, we are opening a Special Issue to compile the latest research in the following topics: innate and/or adaptive immune dysregulation, mechanisms leading to atherosclerosis, potential treatments/ personalized medicine, molecular and/or cellular aspects leading to SLE.

Comprehensive reviews, original articles or short communications are welcome.

We are looking forward to your contributions to this Special Issue.

Dr. Carmelo Carmona-Rivera
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. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly 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 2600 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

  • neutrophils
  • organ damage
  • innate immunity
  • interferon
  • autoimmunity

Published Papers (7 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, Other

15 pages, 2236 KiB  
Article
Rethinking Lupus Nephritis Classification on a Molecular Level
by Salem Almaani, Stephenie D. Prokopec, Jianying Zhang, Lianbo Yu, Carmen Avila-Casado, Joan Wither, James W. Scholey, Valeria Alberton, Ana Malvar, Samir V. Parikh, Paul C. Boutros, Brad H. Rovin and Heather N. Reich
J. Clin. Med. 2019, 8(10), 1524; https://doi.org/10.3390/jcm8101524 - 23 Sep 2019
Cited by 21 | Viewed by 4102
Abstract
The International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus nephritis (LN) classification is under reconsideration, given challenges with inter-rater reliability and resultant inconsistent relationship with treatment response. Integration of molecular classifiers into histologic evaluation can improve diagnostic precision and identify therapeutic targets. This [...] Read more.
The International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus nephritis (LN) classification is under reconsideration, given challenges with inter-rater reliability and resultant inconsistent relationship with treatment response. Integration of molecular classifiers into histologic evaluation can improve diagnostic precision and identify therapeutic targets. This study described the relationship between histological and molecular phenotypes and clinical responses in LN. Renal compartmental mRNA abundance was measured in 54 biopsy specimens from LN patients and correlated to ISN/RPS classification and individual histologic lesions. A subset of transcripts was also evaluated in sequential biopsies of a separate longitudinal cohort of 36 patients with paired samples obtained at the time of flare and at follow up. Unsupervised clustering based on mRNA abundance did not demonstrate a relationship with the (ISN/RPS) classification, nor did univariate statistical analysis. Exploratory analyses suggested a correlation with individual histologic lesions. Glomerular FN1 (fibronectin), SPP1 (secreted phosphoprotein 1), and LGALS3 (galectin 3) abundance correlated with disease activity and changed following treatment. Exploratory analyses suggested relationships between specific transcripts and individual histologic lesions, with the important representation of interferon-regulated genes. Our findings suggested that the current LN classification could be refined by the inclusion of molecular descriptors. Combining molecular and pathologic kidney biopsy phenotypes may hold promise to better classify disease and identify actionable treatment targets and merits further exploration in larger cohorts. Full article
(This article belongs to the Special Issue New Insights into Systemic Lupus Erythematosus: From Immunopathogenesis to Treatment Strategies)
►▼ Show Figures

Figure 1

15 pages, 1597 KiB  
Article
Molecular Profiling of Cutaneous Lupus Lesions Identifies Subgroups Distinct from Clinical Phenotypes
by Celine C. Berthier, Lam C. Tsoi, Tamra J. Reed, Jasmine N. Stannard, Emily M. Myers, Rajaie Namas, Xianying Xing, Stephanie Lazar, Lori Lowe, Matthias Kretzler, Johann E. Gudjonsson and J. Michelle Kahlenberg
J. Clin. Med. 2019, 8(8), 1244; https://doi.org/10.3390/jcm8081244 - 17 Aug 2019
Cited by 44 | Viewed by 4853
Abstract
Cutaneous lupus erythematosus (CLE) is a common manifestation of systemic lupus erythematosus (SLE), and CLE can also develop without systemic involvement. CLE can be difficult to treat and negatively contributes to quality of life. Despite the importance of CLE, our knowledge of what [...] Read more.
Cutaneous lupus erythematosus (CLE) is a common manifestation of systemic lupus erythematosus (SLE), and CLE can also develop without systemic involvement. CLE can be difficult to treat and negatively contributes to quality of life. Despite the importance of CLE, our knowledge of what differentiates cutaneous lupus subtypes is limited. Here, we utilized a large cohort of 90 CLE lesional biopsies to compare discoid lupus erythematosus (DLE) and subacute cutaneous lupus (SCLE) in patients with and without associated SLE in order to discern the drivers of disease activity and possibly uncover better treatment targets. Overall, we found that DLE and SCLE share many differentially expressed genes (DEG) reflecting type I interferon (IFN) signaling and repression of EGFR pathways. No differences between CLE only and SLE-associated CLE lesions were found. Of note, DLE uniquely expresses an IFN-γ node. Unbiased cluster analysis of the DEGs identified two groups separated by neutrophilic vs. monocytic signatures that did not sort the patients based on clinical phenotype or disease activity. This suggests that unbiased analysis of the pathobiology of CLE lesions may be important for personalized medicine and targeted therapeutic decision making. Full article
(This article belongs to the Special Issue New Insights into Systemic Lupus Erythematosus: From Immunopathogenesis to Treatment Strategies)
►▼ Show Figures

Figure 1

13 pages, 253 KiB  
Article
The Impact of Cytokines on the Health-Related Quality of Life in Patients with Systemic Lupus Erythematosus
by Warren David Raymond, Gro Østli Eilertsen, Sharanyaa Shanmugakumar and Johannes Cornelis Nossent
J. Clin. Med. 2019, 8(6), 857; https://doi.org/10.3390/jcm8060857 - 15 Jun 2019
Cited by 8 | Viewed by 2565
Abstract
Introduction: Systemic lupus erythematosus (SLE) reduces the health-related quality of life (HRQoL), even during periods of disease quiescence. We investigated whether subclinical inflammation as reflected by cytokine levels is linked with reduced HRQoL. Methods: A cross-sectional study of SLE patients (n = [...] Read more.
Introduction: Systemic lupus erythematosus (SLE) reduces the health-related quality of life (HRQoL), even during periods of disease quiescence. We investigated whether subclinical inflammation as reflected by cytokine levels is linked with reduced HRQoL. Methods: A cross-sectional study of SLE patients (n = 52, mean age 47.3, 86.5% female) who completed a Short Form Health Survey-36 (SF-36) questionnaire. The clinical and demographic data, scores for the disease activity (SLEDAI-2K), organ damage (SDI), and laboratory data were collected simultaneously. The autoantibody and cytokine levels (IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12, IL-17, BAFF, TNF-α, TGF-β1, MIP-1α, MIP-1β and MCP-1 (levels in pg/mL) were quantified by sandwich ELISA. The comparisons and associations were assessed non-parametrically, and a multiple regression determined the effect sizes (ES) of the variables on the SF-36 domain and summary scores. Results: The SF-36 summary and domain scores for SLE patients were significantly (20–40%) lower than in a comparable control group, with the exception of the Mental Health scores (p = 0.06). SLE patients had a normal body mass index (BMI) (median, 24.2 kg/m2), a high rate of smoking (69.2%), and usage of social security benefits (90.4%). TGF-β1 (ES 0.06), IL-12 (ES −0.11), IFN-γ (ES 0.07) and MCP-1 (ES 0.06) influenced the SF-36 domain scores; and MCP-1 (ES 0.04) influenced the Mental Health Summary Score (MCS). Obvious manifestations, including patient visual analogue scale (VAS) (ES −2.84 to −6.29), alopecia (ES −14.89), malar rash (ES −14.26), and analgesic requirement (ES −19.38), independently influenced the SF-36 items; however, the SF-36 scores were not reflected by the physician VAS or disease activity (SLEDAI-2K). Conclusions: Cytokines had a minimal impact on HRQoL in SLE patients, especially compared to visible skin manifestations, central nervous system (CNS) damage, and pain. Better tools are needed to capture HRQoL in measures of disease activity. Full article
(This article belongs to the Special Issue New Insights into Systemic Lupus Erythematosus: From Immunopathogenesis to Treatment Strategies)

Review

Jump to: Research, Other

20 pages, 735 KiB  
Review
New Horizons in the Genetic Etiology of Systemic Lupus Erythematosus and Lupus-Like Disease: Monogenic Lupus and Beyond
by Erkan Demirkaya, Sezgin Sahin, Micol Romano, Qing Zhou and Ivona Aksentijevich
J. Clin. Med. 2020, 9(3), 712; https://doi.org/10.3390/jcm9030712 - 05 Mar 2020
Cited by 77 | Viewed by 9440
Abstract
Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis [...] Read more.
Systemic lupus erythematosus (SLE) is a clinically and genetically heterogeneous autoimmune disease. The etiology of lupus and the contribution of genetic, environmental, infectious and hormonal factors to this phenotype have yet to be elucidated. The most straightforward approach to unravel the molecular pathogenesis of lupus may rely on studies of patients who present with early-onset severe phenotypes. Typically, they have at least one of the following clinical features: childhood onset of severe disease (<5 years), parental consanguinity, and presence of family history for autoimmune diseases in a first-degree relative. These patients account for a small proportion of patients with lupus but they inform considerable knowledge about cellular pathways contributing to this inflammatory phenotype. In recent years with the aid of new sequencing technologies, novel or rare pathogenic variants have been reported in over 30 genes predisposing to SLE and SLE-like diseases. Future studies will likely discover many more genes with private variants associated to lupus-like phenotypes. In addition, genome-wide association studies (GWAS) have identified a number of common alleles (SNPs), which increase the risk of developing lupus in adult age. Discovery of a possible shared immune pathway in SLE patients, either with rare or common variants, can provide important clues to better understand this complex disorder, it’s prognosis and can help guide new therapeutic approaches. The aim of this review is to summarize the current knowledge of the clinical presentation, genetic diagnosis and mechanisms of disease in patents with lupus and lupus-related phenotypes. Full article
(This article belongs to the Special Issue New Insights into Systemic Lupus Erythematosus: From Immunopathogenesis to Treatment Strategies)
►▼ Show Figures

Figure 1

14 pages, 540 KiB  
Review
Podocyte Injury in Lupus Nephritis
by Hamza Sakhi, Anissa Moktefi, Khedidja Bouachi, Vincent Audard, Carole Hénique, Philippe Remy, Mario Ollero and Khalil El Karoui
J. Clin. Med. 2019, 8(9), 1340; https://doi.org/10.3390/jcm8091340 - 29 Aug 2019
Cited by 39 | Viewed by 6036
Abstract
Systemic lupus erythematosus (SLE) is characterized by a broad spectrum of renal lesions. In lupus glomerulonephritis, histological classifications are based on immune-complex (IC) deposits and hypercellularity lesions (mesangial and/or endocapillary) in the glomeruli. However, there is compelling evidence to suggest that glomerular epithelial [...] Read more.
Systemic lupus erythematosus (SLE) is characterized by a broad spectrum of renal lesions. In lupus glomerulonephritis, histological classifications are based on immune-complex (IC) deposits and hypercellularity lesions (mesangial and/or endocapillary) in the glomeruli. However, there is compelling evidence to suggest that glomerular epithelial cells, and podocytes in particular, are also involved in glomerular injury in patients with SLE. Podocytes now appear to be not only subject to collateral damage due to glomerular capillary lesions secondary to IC and inflammatory processes, but they are also a potential direct target in lupus nephritis. Improvements in our understanding of podocyte injury could improve the classification of lupus glomerulonephritis. Indeed, podocyte injury may be prominent in two major presentations: lupus podocytopathy and glomerular crescent formation, in which glomerular parietal epithelial cells play also a key role. We review here the contribution of podocyte impairment to different presentations of lupus nephritis, focusing on the podocyte signaling pathways involved in these lesions. Full article
(This article belongs to the Special Issue New Insights into Systemic Lupus Erythematosus: From Immunopathogenesis to Treatment Strategies)
►▼ Show Figures

Figure 1

13 pages, 1075 KiB  
Review
The Role of Neutrophils and Neutrophil Extracellular Traps in Vascular Damage in Systemic Lupus Erythematosus
by Liam J. O’Neil, Mariana J. Kaplan and Carmelo Carmona-Rivera
J. Clin. Med. 2019, 8(9), 1325; https://doi.org/10.3390/jcm8091325 - 28 Aug 2019
Cited by 41 | Viewed by 6760
Abstract
Systemic lupus erythematosus (SLE) is an autoimmune syndrome of unknown etiology, characterized by multi-organ inflammation and clinical heterogeneity. SLE affects mostly women and is associated with a high risk of cardiovascular disease. As the therapeutic management of SLE improved, a pattern of early [...] Read more.
Systemic lupus erythematosus (SLE) is an autoimmune syndrome of unknown etiology, characterized by multi-organ inflammation and clinical heterogeneity. SLE affects mostly women and is associated with a high risk of cardiovascular disease. As the therapeutic management of SLE improved, a pattern of early atherosclerotic disease became one of the hallmarks of late disease morbidity and mortality. Neutrophils emerged as important players in SLE pathogenesis and they are associated with increased risk of developing atherosclerotic disease and vascular damage. Enhanced neutrophil extracellular trap (NET) formation was linked to vasculopathy in both SLE and non-SLE subjects and may promote enhanced coronary plaque formation and lipoprotein dysregulation. Foundational work provided insight into the complex relationship between NETs and immune and tissue resident cells within the diseased artery. In this review, we highlight the mechanistic link between neutrophils, NETs, and atherosclerosis within the context of both SLE and non-SLE subjects. We aim to identify actionable pathways that will drive future research toward translational therapeutics, with the ultimate goal of preventing early morbidity and mortality in SLE. Full article
(This article belongs to the Special Issue New Insights into Systemic Lupus Erythematosus: From Immunopathogenesis to Treatment Strategies)
►▼ Show Figures

Figure 1

Other

Jump to: Research, Review

9 pages, 242 KiB  
Brief Report
The State of Lupus Clinical Trials: Minority Participation Needed
by Saira Z. Sheikh, Nicole I. Wanty, Joncel Stephens, Kristen D. Holtz and Sheryl McCalla
J. Clin. Med. 2019, 8(8), 1245; https://doi.org/10.3390/jcm8081245 - 17 Aug 2019
Cited by 17 | Viewed by 4152
Abstract
In the United States, the reported prevalence of lupus is 100,000 to 500,000 patients. Lupus disproportionately affects minority populations, including African Americans and Latinos, and the associated health disparities are substantial. Women are at a higher risk of lupus than men and lupus [...] Read more.
In the United States, the reported prevalence of lupus is 100,000 to 500,000 patients. Lupus disproportionately affects minority populations, including African Americans and Latinos, and the associated health disparities are substantial. Women are at a higher risk of lupus than men and lupus prevalence is the highest in African Americans and Latinos compared to non-Hispanic whites. African Americans and Latinos also have increased disease symptom severity, experience more lupus-related complications, and have a two- to three-fold mortality rate compared to non-Hispanic Whites. Lupus clinical trials offer opportunities for quality care and can result in new treatment options, but African Americans and Latinos are underrepresented in clinical trials because of substantial patient- and provider-side barriers. In conjunction with the limited knowledge of clinical trials that potential participants may have, the healthcare staff approaching participants have limited time to adequately educate and explain the aspects of clinical trials. Indeed, ninety percent of clinical trials fail to meet their recruitment goals on time, so a multi-faceted approach is necessary to address the issue of low minority participation in clinical trials. Full article
(This article belongs to the Special Issue New Insights into Systemic Lupus Erythematosus: From Immunopathogenesis to Treatment Strategies)
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop