Janus Kinase Inhibition and SLE: Is this a Plausible Treatment Option for SLE?

Khalili, Ayida Al; Dutz, Jan P.

doi:10.1007/s40674-020-00155-w

Cited by 3 publications

(12 citation statements)

References 50 publications

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“…Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease characterized by complex pathogenesis that includes genetic factors, environmental triggers, and hormone molecules, as well as an overproduction of an array of cytokines [ 1 ]. Under these conditions a loss of self-tolerance and an overproduction of autoantibodies took place.…”

Section: Introductionmentioning

confidence: 99%

“…Under these conditions a loss of self-tolerance and an overproduction of autoantibodies took place. Both innate and adaptive immune systems have important roles in SLE pathogenesis [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…Type 1 interferons (IFN α and ß, mostly released by dendritic cells) and type 2 IFN (IFN γ -mostly secreted by T cells) are present in SLE. Moreover, an elevated expression of type 1 IFN-regulated genes, known as IFN signature, is considered to be the main characteristic of SLE [ 1 ]. The relationship between JAK/STAT (Janus kinase and Signal Transducers and Activators of Transcription) and IFNs pathway is based on the discovery of type 1 and type 2 IFNs mechanism of action [ 1 , 2 ].…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, an elevated expression of type 1 IFN-regulated genes, known as IFN signature, is considered to be the main characteristic of SLE [ 1 ]. The relationship between JAK/STAT (Janus kinase and Signal Transducers and Activators of Transcription) and IFNs pathway is based on the discovery of type 1 and type 2 IFNs mechanism of action [ 1 , 2 ]. They use JAK/STAT cascade signaling pathway to exert their biological actions [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

“…The relationship between JAK/STAT (Janus kinase and Signal Transducers and Activators of Transcription) and IFNs pathway is based on the discovery of type 1 and type 2 IFNs mechanism of action [ 1 , 2 ]. They use JAK/STAT cascade signaling pathway to exert their biological actions [ 1 ]. Analysis of the inhibition of the JAK/STAT pathway has shown that it has a central role in the decrease of SLE inflammation [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

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Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus?

Richter

Cardoneanu

Burlui

et al. 2022

IJMS

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Systemic lupus erythematosus (SLE) is a chronic, multifactorial autoimmune disease with complex pathogenesis characterized by the imbalance of pro-inflammatory and anti-inflammatory cytokines. Janus kinases (JAKs), intracellular non-receptor tyrosine kinases, are essential for signal pathways of many cytokines. The JAK signal transducers and activators of transcription (STAT) pathways consist of four JAK kinases and seven STATs family members. The dysregulation of JAK-STAT pathways represents an important process in the pathogenesis of SLE. Thus, the use of therapies that target specific signaling pathways would be a challenge in SLE. It is well known that JAK inhibitors have real potential for the treatment of rheumatic diseases, but their efficacy in the treatment of SLE remains to be determined. JAK inhibitors are currently being investigated in phase II and III trials and are considered to become the next stage in SLE therapy. In this review, we report the current data regarding the efficacy of JAK inhibitors in SLE. The development of clinically useful kinase inhibitors might improve upon traditional therapeutic strategies.

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Section: Introductionmentioning

confidence: 99%

“…Under these conditions a loss of self-tolerance and an overproduction of autoantibodies took place. Both innate and adaptive immune systems have important roles in SLE pathogenesis [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus?

Richter

Cardoneanu

Burlui

et al. 2022

IJMS

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Potential Use of Janus Kinase Inhibitors in the Treatment of Systemic Lupus Erythematosus

Huo¹,

Huang²,

Yang³

et al. 2023

JIR

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Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease with unclear pathogenesis. One characteristic of SLE is pro-inflammatory and anti-inflammatory cytokine imbalance. Janus kinase (JAK) is an intracellular non-receptor tyrosine kinase essential for many cytokine signaling pathways. Dysregulation of the JAK/signal transduction and transcriptional activator (STAT) pathway is an important process in SLE pathogenesis. Targeting JAK/STAT proteins can simultaneously block the functions of multiple cytokines. Current SLE treatment with non-specific corticosteroids and immunosuppressants can cause many adverse reactions. Therefore, treatments designed to control specific molecular targets for SLE are desirable. JAK inhibitors (JAKis) are a potential treatment for rheumatic diseases; however, the use of targeted signaling pathways to treat SLE remains a challenge, and its efficacy has not been determined. JAKis have shown positive results in reducing the use of glucocorticoids and/or non-specific immunosuppressants for SLE. JAKis are currently undergoing several clinical trials and expected to be the next stage in the treatment of SLE. Therefore, inhibition of the JAK/STAT pathway through JAKis may improve traditional treatment strategies for SLE.

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Cytokines in Systemic Lupus Erythematosus—Focus on TNF-α and IL-17

Richter,

Macovei,

Mihai

et al. 2023

IJMS

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Systemic lupus erythematosus (SLE) is an autoimmune disorder known for its complex pathogenesis, in which cytokines play an essential role. It seems that the modulation of these cytokines may impact disease progression, being considered potential biomarkers. Thus, TNF (tumor necrosis factor)-α and IL (interleukin)-17 are molecules of great interest in SLE. TNF-α plays a dual role in SLE, with both immunosuppressive and proinflammatory functions. The role of IL-17 is clearly described in the pathogenesis of SLE, having a close association with IL-23 in stimulating the inflammatory response and consecutive tissue destruction. It appears that patients with elevated levels of these cytokines are associated with high disease activity expressed by the SLE disease activity index (SLEDAI) score, although some studies do not confirm this association. However, TNF-α and IL-17 are found in increased titers in lupus patients compared to the general population. Whether inhibition of these cytokines would lead to effective treatment is under discussion. In the case of anti-TNF-α therapies in SLE, the possibility of ATIL (anti-TNF-induced lupus) is a serious concern that limits their use. The use of anti-IL-17 therapies in SLE is a promising option, but not yet approved. Future studies of these cytokines in large cohorts will provide valuable information for the management of SLE.

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Janus Kinase Inhibition and SLE: Is this a Plausible Treatment Option for SLE?

Cited by 3 publications

References 50 publications

Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus?

Why Do We Need JAK Inhibitors in Systemic Lupus Erythematosus?

Potential Use of Janus Kinase Inhibitors in the Treatment of Systemic Lupus Erythematosus

Cytokines in Systemic Lupus Erythematosus—Focus on TNF-α and IL-17

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