Potential for Antigen-Specific Tolerizing Immunotherapy in Systematic Lupus Erythematosus

Thomas, Ranjeny

doi:10.3389/fimmu.2021.654701

Cited by 17 publications

(11 citation statements)

References 177 publications

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“…Restoring immune tolerance has been attempted in a number of autoimmune diseases, including type 1 diabetes mellitus ( 160 ), systemic lupus erythematosus ( 161 ), and neuromyelitis optica ( 162 ). This strategy offers the potentially enormous advantage of leaving host defense completely intact while, in some instances, curing the underlying disease.…”

Section: Emerging Medical Therapies For Tedmentioning

confidence: 99%

Understanding Pathogenesis Intersects With Effective Treatment for Thyroid Eye Disease

Smith

2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context Thyroid eye disease (TED), a vision-threatening and disfiguring autoimmune process, has thwarted our efforts to understand its pathogenesis and develop effective and safe treatments. Recent scientific advances have facilitated improved treatment options. Objective Review historically remote and recent advances in understanding TED. Design/Setting/Participants PubMed was scanned using search terms including thyroid-associated ophthalmopathy, thyroid eye disease, Graves’ orbitopathy, autoimmune thyroid disease, and orbital inflammation. Main outcome measures Strength of scientific evidence, size, scope, and controls of clinical trials/observations. Results Glucocorticoid steroids are widely prescribed systemic medical therapy. They can lessen inflammation-related manifestations of TED but fail to reliably reduce proptosis and diplopia, 2 major causes of morbidity. Other current therapies include mycophenolate, rituximab (anti-CD20 B cell-depleting monoclonal antibody), tocilizumab (interleukin-6 receptor antagonist), and teprotumumab (IGF-I receptor inhibitor). Several new therapeutic approaches have been proposed including targeting prostaglandin receptors, vascular endothelial growth factor, mTOR, and cholesterol pathways. Of potentially greater long-term importance are attempts to restore immune tolerance. Conclusion Despite their current wide use, steroids may no longer enjoy first-tier status for TED as more effective and better tolerated medical options become available. Multiple current and emerging therapies, the rationales for which are rooted in theoretical and experimental science, promise better options. These include teprotumumab, rituximab, and tocilizumab. Restoration of immune tolerance could ultimately become the most effective and safe medical management for TED.

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Section: Emerging Medical Therapies For Tedmentioning

confidence: 99%

Understanding Pathogenesis Intersects With Effective Treatment for Thyroid Eye Disease

Smith

2022

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…There is evidence that low-dose IL-2 therapy can increase the level of Tregs, and because the lack of Tregs may contribute to the pathogenesis of SLE, this may be Frontiers in Pharmacology frontiersin.org an effective treatment for SLE (Tahvildari and Dana, 2019). However, even though IL-2 supplementation significantly increases Treg cells in SLE patients, it does not change the total CD4 + cells (Robinson and Thomas, 2021). This may be because SLE patients have Tregs that secrete less IL-2 and Th1 cells that secrete more IL-2.…”

Section: Discussionmentioning

confidence: 99%

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis

Xiang

Zhang²,

Zhang³

et al. 2022

Front. Pharmacol.

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Objective: Th1 and Th2 cells and their associated cytokines function in the pathogenesis of systemic lupus erythematosus (SLE), but their exact roles are uncertain. We performed a meta-analysis to examine the relationship of these cells and cytokines with SLE.Methods: Multiple databases were searched to identify publications that reported the percentages of Th1 and Th2 cells and their associated cytokines in SLE patients and healthy controls (HCs). Meta-analysis was performed using Stata MP version 16.Results: SLE patients had a lower percentage of Th1 cells, a higher percentage of Th2 cells, and higher levels of Th1- and Th2-associated cytokines than HCs. SLE treatments normalized some but not all of these indicators. For studies in which the proportion of females was less than 94%, the percentage of Th2 cells and the level of IL-10 were higher in patients than HCs. SLE patients who had abnormal kidney function and were younger than 30 years old had a higher proportion of Th1 cells than HCs. SLE patients more than 30 years old had a higher level of IL-6 than HCs.Conclusion: Medications appeared to restore the balance of Th1 cells and other disease indicators in patients with SLE. Gender and age affected the levels of Th1 and Th2 cells, and the abnormally elevated levels of Th2 cells appear to be more pronounced in older patients and males.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42022296540].

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“…Inhibition of various receptor-associated kinases of several pro-inflammatory molecules, including JAK1 and TYK2, has shown promise, and RCT studies are underway to evaluate their efficacy [ 212 ]. Other studies are examining strategies to increase the immunosuppressive activity of regulatory T cells, through their activation by low-dose IL-2 administration [ 213 ]. Table 2 shows the innovative therapies that are still under investigation for possible future treatment of SLE.…”

Section: Future Therapiesmentioning

confidence: 99%

Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus

Accapezzato

Caccavale

Paroli

et al. 2023

IJMS

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Systemic lupus erythematosus (SLE) is a genetically predisposed, female-predominant disease, characterized by multiple organ damage, that in its most severe forms can be life-threatening. The pathogenesis of SLE is complex and involves cells of both innate and adaptive immunity. The distinguishing feature of SLE is the production of autoantibodies, with the formation of immune complexes that precipitate at the vascular level, causing organ damage. Although progress in understanding the pathogenesis of SLE has been slower than in other rheumatic diseases, new knowledge has recently led to the development of effective targeted therapies, that hold out hope for personalized therapy. However, the new drugs available to date are still an adjunct to conventional therapy, which is known to be toxic in the short and long term. The purpose of this review is to summarize recent advances in understanding the pathogenesis of the disease and discuss the results obtained from the use of new targeted drugs, with a look at future therapies that may be used in the absence of the current standard of care or may even cure this serious systemic autoimmune disease.

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Potential for Antigen-Specific Tolerizing Immunotherapy in Systematic Lupus Erythematosus

Cited by 17 publications

References 177 publications

Understanding Pathogenesis Intersects With Effective Treatment for Thyroid Eye Disease

Understanding Pathogenesis Intersects With Effective Treatment for Thyroid Eye Disease

Imbalance of helper T cell type 1, helper T cell type 2 and associated cytokines in patients with systemic lupus erythematosus: A meta-analysis

Advances in the Pathogenesis and Treatment of Systemic Lupus Erythematosus

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