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Novel Advances on Systemic Lupus Erythematosus and Antiphospholipid Syndrome
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Novel Advances on Systemic Lupus Erythematosus and Antiphospholipid Syndrome

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: 20 February 2025 | Viewed by 12128

Special Issue Editor

Prof. Dr. Tatiana M. Reshetnyak

E-Mail Website
Guest Editor
V.A. Nasonova Research Institute of Rheumatology, Moscow, Russia
Interests: systemic lupus erythematosus; antiphospholipid syndrome; IgA antiphospholipid antibodies; neutrophils; thromboembolic complications; spondylitis; immune-mediated inflammatory rheumatic disease

Special Issue Information

Dear Colleagues,

Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects multiple organs and systems in the body. It is characterized by inflammation, pain, and damage to the skin, joints, and other organs. Antiphospholipid syndrome (APS) is a disorder that is associated with SLE, and is characterized by the presence of antiphospholipid antibodies in the blood. These antibodies can cause blood clots, which can lead to stroke, heart attack, and other serious complications.

Antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are interconnected autoimmune diseases. However, in recent years, a sufficient amount of knowledge has been accumulated indicating that APS is a systemic autoimmune thrombo-inflammatory disease. The pathogenesis of these clinical manifestations in APS is not directly related to the development of thrombosis, and these manifestations can persist, progress over time, or occur during appropriate anticoagulation therapy. In some cases, the prescription of immunosuppressive drugs is required, which indicates the role of inflammation in their development. It is important to study the mechanisms of disease development and find new therapeutic targets. In this Special Issue, we will include original research articles and reviews/metanalyses reporting on innovative aspects related to the pathogenesis and clinical manifestations, as well as principles of therapy of patients with SLE and APS. 

Prof. Dr. Tatiana M. Reshetnyak
Guest Editor

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Keywords

  • netosis
  • thromboinflammation
  • thrombosis
  • anticoagulants
  • antiphospholipid syndrome
  • systemic lupus erythematosus

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Published Papers (6 papers)

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Editorial

Jump to: Research, Review

22 pages, 1200 KiB  
Editorial
The Role of Neutrophil Extracellular Traps (NETs) in the Pathogenesis of Systemic Lupus Erythematosus and Antiphospholipid Syndrome
by Tatiana Reshetnyak and Kamila Nurbaeva
Int. J. Mol. Sci. 2023, 24(17), 13581; https://doi.org/10.3390/ijms241713581 - 1 Sep 2023
Cited by 12 | Viewed by 3216
Abstract
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease of unknown aetiology [...] Full article
(This article belongs to the Special Issue Novel Advances on Systemic Lupus Erythematosus and Antiphospholipid Syndrome)
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Research

Jump to: Editorial, Review

20 pages, 4932 KiB  
Article
Parvovirus B19 Infection Is Associated with the Formation of Neutrophil Extracellular Traps and Thrombosis: A Possible Linkage of the VP1 Unique Region
by Bor-Show Tzang, Hao-Yang Chin, Chih-Chen Tzang, Pei-Hua Chuang, Der-Yuan Chen and Tsai-Ching Hsu
Int. J. Mol. Sci. 2024, 25(18), 9917; https://doi.org/10.3390/ijms25189917 - 13 Sep 2024
Viewed by 949
Abstract
Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations [...] Read more.
Neutrophil extracellular traps (NETs) formation, namely NETosis, is implicated in antiphospholipid syndrome (APS)-related thrombosis in various autoimmune disorders such as systemic lupus erythematosus (SLE) and APS. Human parvovirus B19 (B19V) infection is closely associated with SLE and APS and causes various clinical manifestations such as blood disorders, joint pain, fever, pregnancy complications, and thrombosis. Additionally, B19V may trigger the production of autoantibodies, including those against nuclear and phospholipid components. Thus, exploring the connection between B19V, NETosis, and thrombosis is highly relevant. An in vitro NETosis model using differentiated HL-60 neutrophil-like cells (dHL-60) was employed to investigate the effect of B19V-VP1u IgG on NETs formation. A venous stenosis mouse model was used to test how B19V-VP1u IgG-mediated NETs affect thrombosis in vivo. The NETosis was observed in the dHL-60 cells treated with rabbit anti-B19V-VP1u IgG and was inhibited in the presence of either 8-Br-cAMP or CGS216800 but not GSK484. Significantly elevated reactive oxygen species (ROS), myeloperoxidase (MPO), and citrullinated histone (Cit-H3) levels were detected in the dHL60 treated with phorbol myristate acetate (PMA), human aPLs IgG and rabbit anti-B19V-VP1u IgG, respectively. Accordingly, a significantly larger thrombus was observed in a venous stenosis-induced thrombosis mouse model treated with PMA, human aPLs IgG, rabbit anti-B19V-VP1u IgG, and human anti-B19V-VP1u IgG, respectively, along with significantly increased amounts of Cit-H3-, MPO- and CRAMP-positive infiltrated neutrophils in the thrombin sections. This research highlights that anti-B19V-VP1u antibodies may enhance the formation of NETosis and thrombosis and implies that managing and treating B19V infection could lower the risk of thrombosis. Full article
(This article belongs to the Special Issue Novel Advances on Systemic Lupus Erythematosus and Antiphospholipid Syndrome)
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12 pages, 608 KiB  
Article
Association of IL10RA, IL10RB, and IL22RA Polymorphisms/Haplotypes with Susceptibility to and Clinical Manifestations of SLE
by Milka Grk, Rada Miskovic, Ivica Jeremic, Milica Basaric, Marija Dusanovic Pjevic, Biljana Jekic, Danijela Miljanovic, Ivana Lazarevic, Aleksa Despotovic, Andja Cirkovic and Ana Banko
Int. J. Mol. Sci. 2023, 24(14), 11292; https://doi.org/10.3390/ijms241411292 - 10 Jul 2023
Cited by 3 | Viewed by 1581
Abstract
Systemic lupus erythematosus (SLE) is characterized by an imbalance between proinflammatory and anti-inflammatory mediators. Single-nucleotide polymorphisms (SNPs) in genes coding IL10RA, IL10RB, and IL22RA could affect their expression or function and disrupt immune homeostasis. We aimed to analyze the associations of [...] Read more.
Systemic lupus erythematosus (SLE) is characterized by an imbalance between proinflammatory and anti-inflammatory mediators. Single-nucleotide polymorphisms (SNPs) in genes coding IL10RA, IL10RB, and IL22RA could affect their expression or function and disrupt immune homeostasis. We aimed to analyze the associations of IL10RA, IL10RB, and IL22RA polymorphisms/haplotypes with patients’ susceptibility to and clinical manifestations of SLE. Our study included 103 SLE patients and 99 healthy controls. The genotypes of the selected polymorphisms within IL10RA (rs10892202, rs4252270, rs3135932, rs2228055, rs2229113, and rs9610), IL10RB (rs999788, rs2834167, and rs1058867), and IL22RA (rs3795299 and rs16829204) genes were determined by TaqMan® Assays. IL10RB rs1058867 G allele carriers were significantly more frequent among the controls than among the SLE patients (76.8% vs. 61.2%; p = 0.017, OR = 0.477, 95% CI: 0.258–0.879). The IL10RB CAA haplotype was more frequent among the SLE patients than in the control group (42.7% vs. 30.7%; p = 0.027). The IL22RA rs3795299 C allele and rs16829204 CC genotype were associated with Hashimoto thyroiditis in the SLE patients (n = 103; p = 0.002 and p = 0.026, respectively), and in all the included participants (n = 202, p < 0.000 and p = 0.007, respectively), and the IL22RA CC haplotype was more frequent in the SLE patients with Hashimoto thyroiditis (p = 0.047) and in the overall participants with Hashimoto thyroiditis (n = 32, p = 0.004). The IL10RA, IL10RB, and IL22RA polymorphisms/haplotypes could be associated with SLE susceptibility and various clinical manifestations, and the IL22RA CC haplotype could be associated with Hashimoto thyroiditis. Full article
(This article belongs to the Special Issue Novel Advances on Systemic Lupus Erythematosus and Antiphospholipid Syndrome)
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19 pages, 4278 KiB  
Article
Markers of NETosis in Patients with Systemic Lupus Erythematosus and Antiphospholipid Syndrome
by Tatiana Reshetnyak, Kamila Nurbaeva, Ivan Ptashnik, Anna Kudriaeva, Alexey Belogurov, Jr., Aleksandr Lila and Evgeny Nasonov
Int. J. Mol. Sci. 2023, 24(11), 9210; https://doi.org/10.3390/ijms24119210 - 24 May 2023
Cited by 17 | Viewed by 2455
Abstract
Neutrophil Extracellular Traps (NETs) have been implicated in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) pathogenesis. The myeloperoxidase–deoxyribonucleic acid (MPO-DNA) complex and nucleosomes are serum markers of NETosis. The aim of this study was to assess these NETosis parameters as markers for [...] Read more.
Neutrophil Extracellular Traps (NETs) have been implicated in systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) pathogenesis. The myeloperoxidase–deoxyribonucleic acid (MPO-DNA) complex and nucleosomes are serum markers of NETosis. The aim of this study was to assess these NETosis parameters as markers for SLE and APS diagnosis and their association with clinical features and disease activity. A total of 138 people were included in the cross-sectional study: 30 with SLE without APS, 47 with SLE and APS, 41 patients with primary antiphospholipid syndrome (PAPS), and 20 seemingly healthy individuals. Serum MPO-DNA complex and nucleosome levels were determined via an enzyme-linked immunosorbent assay (ELISA). Informed consent was obtained from all subjects involved in the study. The Ethics Committee of the V.A. Nasonova Research Institute of Rheumatology (Protocol No. 25 dated 23 December 2021) approved the study. In patients with SLE without APS, the levels of the MPO-DNA complex were significantly higher compared to patients with SLE with APS, with PAPS, and healthy controls (p < 0.0001). Among patients with a reliable diagnosis of SLE, 30 had positive values of the MPO-DNA complex, of whom 18 had SLE without APS, and 12 had SLE with APS. Patients with SLE and positive MPO-DNA complex levels were significantly more likely to have high SLE activity (χ2 = 5.25, p = 0.037), lupus glomerulonephritis (χ2 = 6.82, p = 0.009), positive antibodies to dsDNA (χ2 = 4.82, p = 0.036), and hypocomplementemia (χ2 = 6.72, p = 0.01). Elevated MPO-DNA levels were observed in 22 patients with APS: 12 with SLE with APS and 10 with PAPS. There were no significant associations between positive levels of the MPO-DNA complex and clinical and laboratory manifestations of APS. The concentration of nucleosomes was significantly lower in the group of SLE patients (±APS) compared to controls and PAPS (p < 0.0001). In SLE patients, the frequency of low nucleosome levels was associated with high SLE activity (χ2 = 13.4, p < 0.0001), lupus nephritis (χ2 = 4.1, p = 0.043), and arthritis (χ2 = 3.89, p = 0.048). An increase in the specific marker of NETosis, the MPO-DNA complex, was found in the blood serum of SLE patients without APS. Elevated levels of the MPO-DNA complex can be regarded as a promising biomarker of lupus nephritis, disease activity, and immunological disorders in SLE patients. Lower levels of nucleosomes were significantly associated with SLE (±APS). Low nucleosome levels were more common in patients with high SLE activity, lupus nephritis, and arthritis. Full article
(This article belongs to the Special Issue Novel Advances on Systemic Lupus Erythematosus and Antiphospholipid Syndrome)
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Review

Jump to: Editorial, Research

23 pages, 1841 KiB  
Review
Antiphospholipid Antibodies as Key Players in Systemic Lupus Erythematosus: The Relationship with Cytokines and Immune Dysregulation
by Patricia Richter, Minerva Codruta Badescu, Ciprian Rezus, Anca Ouatu, Nicoleta Dima, Diana Popescu, Alexandra Maria Burlui, Ioana Bratoiu, Ioana Ruxandra Mihai and Elena Rezus
Int. J. Mol. Sci. 2024, 25(20), 11281; https://doi.org/10.3390/ijms252011281 - 20 Oct 2024
Viewed by 934
Abstract
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by an overproduction of cytokines, such as interleukins and interferons, contributing to systemic inflammation and tissue damage. Antiphospholipid syndrome is a thrombo-inflammatory autoimmune disease affecting a third of SLE patients. We performed an [...] Read more.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by an overproduction of cytokines, such as interleukins and interferons, contributing to systemic inflammation and tissue damage. Antiphospholipid syndrome is a thrombo-inflammatory autoimmune disease affecting a third of SLE patients. We performed an in-depth analysis of the available literature, and we highlighted the complex interplay between immunity, inflammation, and thrombosis, the three major pathogenic pathways that are trapped in a mutually reinforcing destructive loop. Full article
(This article belongs to the Special Issue Novel Advances on Systemic Lupus Erythematosus and Antiphospholipid Syndrome)
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29 pages, 1365 KiB  
Review
CAR-T-Cell Therapy for Systemic Lupus Erythematosus: A Comprehensive Overview
by Haneen M. Abdalhadi, Walter W. Chatham and Fatima K. Alduraibi
Int. J. Mol. Sci. 2024, 25(19), 10511; https://doi.org/10.3390/ijms251910511 - 29 Sep 2024
Viewed by 2251
Abstract
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by the production of autoreactive B and T cells and cytokines, leading to chronic inflammation affecting multiple organs. SLE is associated with significant complications that substantially increase morbidity and mortality. Given its complex [...] Read more.
Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by the production of autoreactive B and T cells and cytokines, leading to chronic inflammation affecting multiple organs. SLE is associated with significant complications that substantially increase morbidity and mortality. Given its complex pathogenesis, conventional treatments for SLE often have significant side effects and limited efficacy, necessitating the exploration of novel therapeutic strategies. One promising approach is the use of chimeric antigen receptor (CAR)-T-cell therapy, which has shown remarkable success in treating refractory hematological malignancies. This review provides a comprehensive analysis of the current use of CAR-T-cell therapy in SLE. Full article
(This article belongs to the Special Issue Novel Advances on Systemic Lupus Erythematosus and Antiphospholipid Syndrome)
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