Systemic lupus erythematosus (SLE): emerging therapeutic targets

Mathias, Lauren; Stohl, William

doi:10.1080/14728222.2020.1832464

Cited by 27 publications

(24 citation statements)

References 159 publications

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“…Apart from all these, any dysregulation in B cells that produces proinflammatory cytokines (i.e., IL-1, IL-3, IL-6, IL-23, and TNF- α ) pushes the inflammatory events and drives the SLE disease. Thus, targeting these B and T cells could be proved as a therapeutic advantage to control SLE [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

[Retracted] Identification of Peptides as Novel Inhibitors to Target IFN‐γ, IL‐3, and TNF‐α in Systemic Lupus Erythematosus

Mustafa

Mahrosh

Salman

et al. 2021

BioMed Research International

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Autoimmune disorder is a chronic immune imbalance which is developed through a series of pathways. The defect in B cells, T cells, and lack of self-tolerance has been greatly associated with the onset of many types of autoimmune complications including rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and chronic inflammatory demyelinating polyneuropathy. The SLE is an autoimmune disease with a common type of lupus that causes tissue and organ damage due to the wide spread of inflammation. In the current study, twenty anti-inflammatory peptides derived from plant and animal sources were docked as ligands or peptides counter to proinflammatory cytokines. Interferon gamma (IFN-γ), interleukin 3 (IL-3), and tumor necrosis factor alpha (TNF-α) were targeted in this study as these are involved in the pathogenesis of SLE in many clinical studies. Two docking approaches (i.e., protein-ligand docking and peptide-protein docking) were employed in this study using Molecular Operating Environment (MOE) software and HADDOCK web server, respectively. Amongst docked twenty peptides, the peptide DEDTQAMMPFR with S -score of -11.3018 and HADDOCK score of − 10.3 ± 2.5 kcal/mol showed the best binding interactions and energy validation with active amino acids of IFN-γ protein in both docking approaches. Depending upon these results, this peptide could be used as a potential drug candidate to target IFN-γ, IL-3, and TNF-α proteins to control inflammatory events. Other peptides (i.e., QEPQESQQ and FRDEHKK) also revealed good binding affinity with IFN-γ with S -scores of -10.98 and -10.55, respectively. Similarly, the peptides KHDRGDEF, FRDEHKK, and QEPQESQQ showed best binding interactions with IL-3 with S -scores of -8.81, -8.64, and -8.17, respectively.

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Section: Introductionmentioning

confidence: 99%

[Retracted] Identification of Peptides as Novel Inhibitors to Target IFN‐γ, IL‐3, and TNF‐α in Systemic Lupus Erythematosus

Mustafa

Mahrosh

Salman

et al. 2021

BioMed Research International

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“…Several investigators suggested that targeting IL-12, IL-23, and IL-17 could be a therapeutic option in SLE, since modulation of this pathway may also have regulatory effect on the IFN system via indirect mechanisms [ 82 ]. This hypothesis is under investigation.…”

Section: Il-12 Il-17 and Il-23mentioning

confidence: 99%

Cytokines as Biomarkers in Systemic Lupus Erythematosus: Value for Diagnosis and Drug Therapy

Idborg

Oke

2021

IJMS

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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease. The disease is characterized by activation and dysregulation of both the innate and the adaptive immune systems. The autoimmune response targets self-molecules including cell nuclei, double stranded DNA and other intra and extracellular structures. Multiple susceptibility genes within the immune system have been identified, as well as disturbances in different immune pathways. SLE may affect different organs and organ systems, and organ involvement is diverse among individuals. A universal understanding of pathophysiological mechanism of the disease, as well as directed therapies, are still missing. Cytokines are immunomodulating molecules produced by cells of the immune system. Interferons (IFNs) are a broad group of cytokines, primarily produced by the innate immune system. The IFN system has been observed to be dysregulated in SLE, and therefore IFNs have been extensively studied with a hope to understand the disease mechanisms and identify novel targeted therapies. In several autoimmune diseases identification and subsequent blockade of specific cytokines has led to successful therapies, for example tumor necrosis factor-alpha (TNF-α) inhibition in rheumatoid arthritis. Authors of this review have sought corresponding developments in SLE. In the current review, we cover the actual knowledge on IFNs and other studied cytokines as biomarkers and treatment targets in SLE.

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“…66 The disease is characterized by altered B-cell selection, triggering production of autoreactive antibodies and pro-inflammatory cytokines, and the presentation of autoantigens to autoreactive T cells. 65 Due to the heterogeneity in the etiopathogenesis of SLE, numerous therapeutic targets have been investigated, 67 119 The role of eosinophils is debated, but eosinophil proteins may promote mast cell degranulation in CSU, and eosinopenia has been linked to high disease activity, type IIb autoimmunity, and poor response to treatment. 120 In addition to its well-established role in B-cell signaling, evidence suggests that BTK is specifically required for IgE-mediated activation of basophils 37 and in MC FcεRI-induced cytokine secretion.…”

Section: Other Skin Conditionsmentioning

confidence: 99%

Bruton's tyrosine kinase inhibition—An emerging therapeutic strategy in immune‐mediated dermatological conditions

Mendes‐Bastos

Brasileiro

Kolkhir

et al. 2022

Allergy

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Bruton's tyrosine kinase (BTK), a member of the Tec kinase family, is critically involved in a range of immunological pathways. The clinical application of BTK inhibitors for B-cell malignancies has proven successful, and there is strong rationale for the potential benefits of BTK inhibitors in some autoimmune and allergic conditions, including immune-mediated dermatological diseases. However, the established risk-to-benefit profile of "first-generation" BTK inhibitors cannot be extrapolated to these emerging, non-oncological, indications. "Next-generation" BTK inhibitors such as remibrutinib and fenebrutinib entered clinical development for chronic spontaneous urticaria (CSU); rilzabrutinib and tirabrutinib are being studied as potential treatments for pemphigus. Promising data from early-phase clinical trials in CSU suggest potential for these agents to achieve strong pathway inhibition, which may translate into measurable clinical benefits, as well as other effects such as the disruption of autoantibody production. BTK inhibitors may help to overcome some of the shortcomings of monoclonal antibody treatments for immune-mediated dermatological conditions such as CSU, pemphigus, and systemic lupus erythematosus. In addition, the use of BTK inhibitors may improve understanding of the pathophysiological roles of mast cells, basophils, and B cells in such conditions.

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Systemic lupus erythematosus (SLE): emerging therapeutic targets

Cited by 27 publications

References 159 publications

[Retracted] Identification of Peptides as Novel Inhibitors to Target IFN‐γ, IL‐3, and TNF‐α in Systemic Lupus Erythematosus

[Retracted] Identification of Peptides as Novel Inhibitors to Target IFN‐γ, IL‐3, and TNF‐α in Systemic Lupus Erythematosus

Cytokines as Biomarkers in Systemic Lupus Erythematosus: Value for Diagnosis and Drug Therapy

Bruton's tyrosine kinase inhibition—An emerging therapeutic strategy in immune‐mediated dermatological conditions

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