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Technological and Molecular Advances in Systemic Lupus Erythematosus
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Technological and Molecular Advances in Systemic Lupus Erythematosus

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 30 May 2024 | Viewed by 12698

Special Issue Editor

Prof. Dr. Chi Chiu Mok

E-Mail Website
Guest Editor
Department of Medicine, Tuen Mun Hospital, New Territories 999077, Hong Kong, China
Interests: lupus; biologics; biomarkers; therapeutics; osteoporosis; rheumatoid arthritis; lupus nephritis; targeted therapies

Special Issue Information

Dear Colleagues,

It is my pleasure to edit a special issue on technological and molecular advances in Systemic Lupus Erythematosus (SLE) for International Journal of molecular science (IJMS). SLE is a clinical and immunological heterogeneous disease that is associated with varying manifestations and treatment response and prognosis. Patient stratification to enhance treatment efficacy and reduce medication related toxicities is a major developmental goal. This issue targets a broad range of topics that are relevant for personalized medicine in SLE. Review and original articles on the following list of topics that are related to patient stratification to receive tailored therapies are welcome. Articles are expected to highlight the advances in laboratory and imaging techniques instead of purely clinical perspectives. Topics include, but not limited, the following.

  1. Imaging advances, artificial intelligence and telemedicine for the diagnosis and evaluation of SLE
  2. Molecular profiling in SLE (genomics, proteomics, metabolomics and biomarkers)
  3. Cellular and molecular therapies in SLE (eg. mesenchymal cell, stem cell transplantation, CAR-T cell therapies)

Prof. Dr. Chi Chiu Mok
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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
  • SLE
  • autoreactive lymphocytes
  • antoantibodies
  • lupus nephritis
  • immunological heterogeneous
  • genomics
  • proteomics
  • metabolomics
  • biomarkers
  • cellular and molecular therapies
  • stem cell transplantation
  • CAR-T cell therapies
  • biologic therapy
  • imaging diagnosis
  • treatment strategies

Published Papers (6 papers)

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Research

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11 pages, 1871 KiB  
Article
Urinary Long Non-Coding RNA Levels as Biomarkers of Lupus Nephritis
by Cheuk-Chun Szeto, Ho So, Peter Yam-Kau Poon, Cathy Choi-Wan Luk, Jack Kit-Chung Ng, Winston Wing-Shing Fung, Gordon Chun-Kau Chan, Kai-Ming Chow, Fernand Mac-Moune Lai and Lai-Shan Tam
Int. J. Mol. Sci. 2023, 24(14), 11813; https://doi.org/10.3390/ijms241411813 - 22 Jul 2023
Cited by 2 | Viewed by 1419
Abstract
Background: Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis. Method: We studied three cohorts of lupus nephritis patients (31, [...] Read more.
Background: Emerging evidence suggests that long non-coding RNA (lncRNA) plays important roles in the regulation of gene expression. We determine the role of using urinary lncRNA as a non-invasive biomarker for lupus nephritis. Method: We studied three cohorts of lupus nephritis patients (31, 78, and 12 patients, respectively) and controls (6, 7, and 24 subjects, respectively). The urinary sediment levels of specific lncRNA targets were studied using real-time quantitative polymerase chain reactions. Results: The severity of proteinuria inversely correlated with urinary maternally expressed gene 3 (MEG3) (r = −0.423, p = 0.018) and ANRIL levels (r = −0.483, p = 0.008). Urinary MEG3 level also inversely correlated with the SLEDAI score (r = −0.383, p = 0.034). Urinary cancer susceptibility candidate 2 (CASC2) levels were significantly different between histological classes of nephritis (p = 0.026) and patients with pure class V nephritis probably had the highest levels, while urinary metastasis-associated lung carcinoma transcript 1 (MALAT1) level significantly correlated with the histological activity index (r = −0.321, p = 0.004). Urinary taurine-upregulated gene 1 (TUG1) level was significantly lower in pure class V lupus nephritis than primary membranous nephropathy (p = 0.003) and minimal change nephropathy (p = 0.04), and urinary TUG1 level correlated with eGFR in class V lupus nephritis (r = 0.706, p = 0.01). Conclusions: We identified certain urinary lncRNA targets that may help the identification of lupus nephritis and predict the histological class of nephritis. Our findings indicate that urinary lncRNA levels may be developed as biomarkers for lupus nephritis. Full article
(This article belongs to the Special Issue Technological and Molecular Advances in Systemic Lupus Erythematosus)
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17 pages, 2271 KiB  
Article
Neural Regeneration in Dry Eye Secondary to Systemic Lupus Erythematosus Is Also Disrupted like in Rheumatoid Arthritis, but in a Progressive Fashion
by Balázs Sonkodi, László Marsovszky, Anita Csorba, Attila Balog, Bence Kopper, Zoltán Zsolt Nagy and Miklós D. Resch
Int. J. Mol. Sci. 2023, 24(13), 10680; https://doi.org/10.3390/ijms241310680 - 26 Jun 2023
Cited by 3 | Viewed by 1776
Abstract
Our objective in this study was to analyze the aberrant neural regeneration activity in the cornea by means of in vivo confocal microscopy in systemic lupus erythematosus patients with concurrent dry eye disease. We examined 29 systemic lupus erythematosus patients and 29 age-matched [...] Read more.
Our objective in this study was to analyze the aberrant neural regeneration activity in the cornea by means of in vivo confocal microscopy in systemic lupus erythematosus patients with concurrent dry eye disease. We examined 29 systemic lupus erythematosus patients and 29 age-matched healthy control subjects. Corneal nerve fiber density (CNFD, the number of fibers/mm2) and peripheral Langerhans cell morphology were lower (p < 0.05) in systemic lupus erythematosus patients compared to the control group. Interestingly, corneal nerve branch density, corneal nerve fiber length, corneal nerve fiber total branch density, and corneal nerve fiber area showed a negative correlation with disease duration. A negative correlation was also demonstrated between average corneal nerve fiber density and central Langerhans cell density. This is in line with our hypothesis that corneal somatosensory terminal Piezo2 channelopathy-induced impaired Piezo2–Piezo1 crosstalk not only disrupts regeneration and keeps transcription activated, but could lead to Piezo1 downregulation and cell activation on Langerhans cells when we consider a chronic path. Hence, Piezo2 containing mechanosensory corneal nerves and dendritic Langerhans cells could also be regarded as central players in shaping the ocular surface neuroimmune homeostasis through the Piezo system. Moreover, lost autoimmune neuroinflammation compensation, lost phagocytic self-eating capacity, and lost transcription regulation, not to mention autoantibodies against vascular heparin sulfate proteoglycans and phospholipids, could all contribute to the progressive fashion of dry eye disease in systemic lupus erythematosus. Full article
(This article belongs to the Special Issue Technological and Molecular Advances in Systemic Lupus Erythematosus)
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18 pages, 1005 KiB  
Article
Interaction between Long Noncoding RNAs and Syncytin-1/Syncytin-2 Genes and Transcripts: How Noncoding RNAs May Affect Pregnancy in Patients with Systemic Lupus Erythematosus
by Rossella Talotta
Int. J. Mol. Sci. 2023, 24(3), 2259; https://doi.org/10.3390/ijms24032259 - 23 Jan 2023
Cited by 1 | Viewed by 1705
Abstract
Background: Patients with systemic lupus erythematosus (SLE) often suffer from obstetric complications not necessarily associated with the antiphospholipid syndrome. These events may potentially result from the reduced placental synthesis of the fusogenic proteins syncytin-1 and syncytin-2, observed in women with pregnancy-related disorders. SLE [...] Read more.
Background: Patients with systemic lupus erythematosus (SLE) often suffer from obstetric complications not necessarily associated with the antiphospholipid syndrome. These events may potentially result from the reduced placental synthesis of the fusogenic proteins syncytin-1 and syncytin-2, observed in women with pregnancy-related disorders. SLE patients have an aberrant noncoding (nc)RNA signature that may in turn dysregulate the expression of syncytin-1 and syncytin-2 during placentation. The aim of this research is to computationally evaluate and characterize the interaction between syncytin-1 and syncytin-2 genes and human ncRNAs and to discuss the potential implications for SLE pregnancy adverse outcomes. Methods: The FASTA sequences of the syncytin-1 and syncytin-2 genes were used as inputs to the Ensembl.org library to find any alignments with human ncRNA genes and their transcripts, which were characterized for their tissue expression, regulatory activity on adjacent genes, biological pathways, and potential association with human disease. Results: BLASTN analysis revealed a total of 100 hits with human long ncRNAs (lncRNAs) for the syncytin-1 and syncytin-2 genes, with median alignment scores of 151 and 66.7, respectively. Only lncRNAs TP53TG1, TTTY14, and ENSG00000273328 were reported to be expressed in placental tissue. Dysregulated expression of lncRNAs TP53TG1, LINC01239, and LINC01320 found in this analysis has previously been described in SLE patients as well as in women with a high-risk pregnancy. In addition, some of the genes adjacent to lncRNAs aligned with syncytin-1 or syncytin-2 in a regulatory region might increase the risk of pregnancy complications or SLE. Conclusions: This is the first computational study showing alignments between syncytin-1 and syncytin-2 genes and human lncRNAs. Whether this mechanism affects syncytiotrophoblast morphogenesis in SLE females is unknown and requires further investigation. Full article
(This article belongs to the Special Issue Technological and Molecular Advances in Systemic Lupus Erythematosus)
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Review

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26 pages, 2916 KiB  
Review
Helios as a Potential Biomarker in Systemic Lupus Erythematosus and New Therapies Based on Immunosuppressive Cells
by Andrés París-Muñoz, Odelaisy León-Triana, Antonio Pérez-Martínez and Domingo F. Barber
Int. J. Mol. Sci. 2024, 25(1), 452; https://doi.org/10.3390/ijms25010452 - 29 Dec 2023
Cited by 1 | Viewed by 1478
Abstract
The Helios protein (encoded by the IKZF2 gene) is a member of the Ikaros transcription family and it has recently been proposed as a promising biomarker for systemic lupus erythematosus (SLE) disease progression in both mouse models and patients. Helios is beginning to [...] Read more.
The Helios protein (encoded by the IKZF2 gene) is a member of the Ikaros transcription family and it has recently been proposed as a promising biomarker for systemic lupus erythematosus (SLE) disease progression in both mouse models and patients. Helios is beginning to be studied extensively for its influence on the T regulatory (Treg) compartment, both CD4+ Tregs and KIR+/Ly49+ CD8+ Tregs, with alterations to the number and function of these cells correlated to the autoimmune phenomenon. This review analyzes the most recent research on Helios expression in relation to the main immune cell populations and its role in SLE immune homeostasis, specifically focusing on the interaction between T cells and tolerogenic dendritic cells (tolDCs). This information could be potentially useful in the design of new therapies, with a particular focus on transfer therapies using immunosuppressive cells. Finally, we will discuss the possibility of using nanotechnology for magnetic targeting to overcome some of the obstacles related to these therapeutic approaches. Full article
(This article belongs to the Special Issue Technological and Molecular Advances in Systemic Lupus Erythematosus)
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16 pages, 888 KiB  
Review
Application of Machine Learning Models in Systemic Lupus Erythematosus
by Fulvia Ceccarelli, Francesco Natalucci, Licia Picciariello, Claudia Ciancarella, Giulio Dolcini, Angelica Gattamelata, Cristiano Alessandri and Fabrizio Conti
Int. J. Mol. Sci. 2023, 24(5), 4514; https://doi.org/10.3390/ijms24054514 - 24 Feb 2023
Cited by 5 | Viewed by 2973
Abstract
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease and is extremely heterogeneous in terms of immunological features and clinical manifestations. This complexity could result in a delay in the diagnosis and treatment introduction, with impacts on long-term outcomes. In this view, the [...] Read more.
Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease and is extremely heterogeneous in terms of immunological features and clinical manifestations. This complexity could result in a delay in the diagnosis and treatment introduction, with impacts on long-term outcomes. In this view, the application of innovative tools, such as machine learning models (MLMs), could be useful. Thus, the purpose of the present review is to provide the reader with information about the possible application of artificial intelligence in SLE patients from a medical perspective. To summarize, several studies have applied MLMs in large cohorts in different disease-related fields. In particular, the majority of studies focused on diagnosis and pathogenesis, disease-related manifestations, in particular Lupus Nephritis, outcomes and treatment. Nonetheless, some studies focused on peculiar features, such as pregnancy and quality of life. The review of published data demonstrated the proposal of several models with good performance, suggesting the possible application of MLMs in the SLE scenario. Full article
(This article belongs to the Special Issue Technological and Molecular Advances in Systemic Lupus Erythematosus)
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Other

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11 pages, 1126 KiB  
Brief Report
Doubtful Clinical Value of Subtyping Anti-U1-RNP Antibodies Regarding the RNP-70 kDa Antigen in Sera of Patients with Systemic Lupus Erythematosus
by Awais Ahmad, André Brylid, Charlotte Dahle, Muna Saleh, Örjan Dahlström, Helena Enocsson and Christopher Sjöwall
Int. J. Mol. Sci. 2023, 24(12), 10398; https://doi.org/10.3390/ijms241210398 - 20 Jun 2023
Cited by 1 | Viewed by 2408
Abstract
The detection of antinuclear antibodies is central to the diagnosis and prognosis of systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) and mixed connective tissue disease (MCTD). Anti-U1-RNP and anti-RNP70 antibodies were assayed in the sera of patients with SLE (n = [...] Read more.
The detection of antinuclear antibodies is central to the diagnosis and prognosis of systemic lupus erythematosus (SLE), primary Sjögren’s syndrome (pSS) and mixed connective tissue disease (MCTD). Anti-U1-RNP and anti-RNP70 antibodies were assayed in the sera of patients with SLE (n = 114), pSS (n = 54) and MCTD (n = 12). In the SLE group, 34/114 (30%) were anti-U1-RNP positive, and 21/114 (18%) were both anti-RNP70 positive and anti-U1-RNP positive. In the MCTD group, 10/12 (83%) were anti-U1-RNP positive, and 9/12 (75%) were anti-RNP70 positive. Only one individual with pSS was antibody positive (for both anti-U1-RNP and anti-RNP70). All anti-RNP70-positive samples were also anti-U1-RNP positive. Anti-U1-RNP-positive subjects with SLE were younger (p < 0.0001); showed lower concentrations of complement protein 3 (p = 0.03); had lower eosinophil (p = 0.0005), lymphocyte (p = 0.006) and monocyte (p = 0.03) counts; and had accrued less organ damage (p = 0.006) than the anti-U1-RNP-negative SLE patients. However, we observed no significant clinical or laboratory parameter differences between the anti-U1-RNP-positive individuals with/without anti-RNP70 in the SLE group. In conclusion, anti-RNP70 antibodies are not exclusive to MCTD but are rarely detected in pSS and healthy individuals. In SLE, anti-U1-RNP antibodies are associated with a clinical phenotype that resembles MCTD, with hematologic involvement and less damage accrual. Based on our results, the clinical value of subtyping anti-RNP70 in anti-U1-RNP-positive sera appears to be of limited value. Full article
(This article belongs to the Special Issue Technological and Molecular Advances in Systemic Lupus Erythematosus)
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