Anti-IFNαR Mabs for the treatment of systemic lupus erythematosus

Goulden, Bethan; Isenberg, David

doi:10.1080/14712598.2021.1841164

Cited by 14 publications

(18 citation statements)

References 62 publications

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“…This is the strategy behind anifrolumab, a fully human monoclonal antibody against the type I IFN receptor subunit 1 [171,172]. The drug is well-tolerated and was found to improve plasma cholesterol efflux capacity in a randomized placebo-controlled study of SLE patients [68,173].…”

Section: Novel Therapeuticsmentioning

confidence: 99%

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention

et al. 2021

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Systemic lupus erythematosus (SLE) carries a significant risk of cardiovascular disease (CVD). The prevalence of premature CVD is especially noteworthy because it occurs in premenopausal women with SLE who would otherwise have very low rates of CVD. While traditional risk factors likely play a role in development of CVD in the setting of SLE, they do not fully explain the excess risk. The pathogenesis of CVD in SLE is not fully understood, but the inflammatory nature of SLE is believed to be a key factor in accelerating atherosclerosis. Systemic inflammation may lead to an abnormal lipid profile with elevated triglycerides, total cholesterol, and low-density lipoprotein cholesterol and dysfunctional high-density lipoprotein cholesterol. Additionally, the inflammatory milieu of SLE plasma promotes endothelial dysfunction and vascular injury, early steps in the progression of atherosclerotic CVD. Despite the overall headway that has been achieved in treating lupus, innovative therapeutics specifically targeting the progression of atherosclerosis within the lupus population are currently lacking. However, there have been advancements in the development of promising modalities for diagnosis of subclinical atherosclerosis and detection of high CVD risk patients. Due to the significant impact of CVD on morbidity and mortality, research addressing prevention and treatment of CVD in SLE needs to be prioritized. This review explores the intricate interplay of SLE-specific properties that contribute to atherosclerosis and CVD within this population, as well as screening methods and possible therapies.

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Section: Novel Therapeuticsmentioning

confidence: 99%

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention

et al. 2021

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“…11 Recent data from randomised controlled trials show that blocking the type I IFN receptor by anifrolumab decreases global disease activity in SLE. 12 Corresponding studies in pSS are lacking but a phase I open-label study in SSc has been conducted, and recent studies indicate that type I IFN signalling is important also in SSc. [13][14][15] Another similarity between the three diseases is the high prevalence of autoantibodies, for example, antibodies targeting cellular antigens referred to as ANA usually detected by immunofluorescence (IF) microscopy on HEp-2 cells and/or antigen-specific assays.…”

Section: How This Study Might Affect Research Practice or Policymentioning

confidence: 99%

Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjögren’s syndrome and systemic sclerosis

et al. 2022

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ObjectiveSLE, primary Sjögren’s syndrome (pSS) and systemic sclerosis (SSc) are heterogeneous autoimmune diseases with a dysregulated type I interferon (IFN) system. The diseases often show overlapping clinical manifestations, which may result in diagnostic challenges. We asked to which extent SSc-associated autoantibodies are present in SLE and pSS, and whether these link to serum IFN-α, clinical phenotypes and sex. Samples with clinical data from patients with SSc and healthy blood donors (HBDs) served as controls. Finally, the diagnostic performance of SSc-associated autoantibodies was evaluated.MethodsSamples from well-characterised subjects with SLE (n=510), pSS (n=116), SSc (n=57) and HBDs (n=236) were analysed using a commercially available immunoassay (EuroLine Systemic Sclerosis Profile (IgG)). IFN-α was quantified by ELISA. Self-reported data on Raynaud’s phenomenon (RP) were available.ResultsWith exceptions for anti-Ro52/SSA and anti-Th/To, SSc-associated autoantibodies were more frequent in SSc than in SLE, pSS and HBDs regardless of sex. IFN-α levels correlated with the number of positive SSc-associated autoantibodies (r=0.29, p<0.0001) and associated with Ro52/SSA positivity (p<0.0001). By using data from SLE, SSc and HBDs, RP was significantly associated with topoisomerase I, centromere protein (CENP)-B, RNA polymerase III 11 kDa, RNA polymerase III 155 kDa and PM-Scl100 whereas Ro52/SSA associated inversely with RP. In SLE, CENP-A was associated with immunological disorder, CENP-B with serositis and Ku with lupus nephritis. By combining analysis of ANA (immunofluorescence) with SSc-associated autoantibodies, the diagnostic sensitivity reached 98% and the specificity 33%.ConclusionsThe 13 specificities included in the EuroLine immunoassay are commonly detected in SSc, but they are also frequent among individuals with other diseases imprinted by type I IFNs. These findings are valuable when interpreting serological data on patients with suspected SSc, especially as patients may present with disease manifestations overlapping different rheumatological diseases. In SLE, we observed associations between manifestations and SSc-associated autoantibodies which have not previously been reported.

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“…В свою очередь НК и ИК, связываясь с TLR7 и TLR9, локализованными в эндосомах плазмоцитоидных дендритных клеток (ДК), индуцируют синтез ИФН типа I (а также ИФН типа III). Комплекс данных, полученных в процессе фундаментальных и клинических исследований, послужил основанием для разработки нового подхода к фармакотерапии СКВ, связанного с использованием мАТ, блокирующих активность рецепторов ИФН типа I [162][163][164]. В ряду этих препаратов особое место занимает анифролумаб (АФМ), представляющий собой человеческие мАТ к IgG1, блокирующие рецептор ИФН-α -IFNAR1 (Interferon Alpha and Beta Receptor Subunit 1) с высокой афинностью и специфичностью [91,165,166].…”

Section: проблемы системной красной волчанки в XXI векеunclassified

Systemic lupus erythematosus: history and modernity

Насонов

Soloviev²,

Arshinov

2022

Naučno-praktičeskaâ revmatologiâ

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Systemic lupus erythematosus (SLE) is a systemic autoimmune rheumatic disease of unknown etiology, characterized by hyperproduction of non-organ-specific autoantibodies to various components of the cell nucleus and the development of immune-inflammatory damage to internal organs. Currently, SLE is considered as a prototype of a systemic human autoimmune pathology, the central mechanism of immunopathogenesis of which is a violation of immunological tolerance to self-antigens, due to a complex interaction of genetic, epigenetic, environmental factors. The publication discusses the history of the study of SLE, the contribution of Russian scientists (V.A. Nasonova and others) to the study of th is problem, current trends in clinical and scientific research related to the improvement of diagnostic criteria and pharmacotherapy of this disease.

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Anti-IFNαR Mabs for the treatment of systemic lupus erythematosus

Cited by 14 publications

References 62 publications

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention

Understanding Accelerated Atherosclerosis in Systemic Lupus Erythematosus: Toward Better Treatment and Prevention

Autoantibodies associated with systemic sclerosis in three autoimmune diseases imprinted by type I interferon gene dysregulation: a comparison across SLE, primary Sjögren’s syndrome and systemic sclerosis

Systemic lupus erythematosus: history and modernity

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