Monocyte type I interferon signature in antiphospholipid syndrome is related to proinflammatory monocyte subsets, hydroxychloroquine and statin use

Hoogen, Lucas L van den; Fritsch-Stork, Ruth; Versnel, Marjan A.; Derksen, R. H. W. M.; Roon, Joël A G van; Radstake, Timothy R D J

doi:10.1136/annrheumdis-2016-210485

Cited by 51 publications

(31 citation statements)

References 12 publications

(15 reference statements)

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“…Interestingly, a number of the upregulated genes have already been defined as playing a role in APS, such as TLR4 (13), the complement component 5a receptor (47), protease-activated receptor 2 (48), and Fms-related tyrosine kinase 1 (FLT1, a receptor for vascular endothelial growth factor) (49). Furthermore, TLR and IFN-mediated signaling stood out in the meta-group analysis -both are receiving active attention in APS (50)(51)(52)(53).…”

Section: Discussionmentioning

confidence: 99%

Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

et al. 2017

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Section: Discussionmentioning

confidence: 99%

Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

et al. 2017

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“…Additionally, and probably most appreciated, a large number of patients suffering from one of these three diseases present with a so-called type I interferon signature. As such, there is clear evidence for commonly shared pathogenic activation of molecular pathways [1][2][3][4]. In contrast, these SADs are clinically quite distinct.…”

Section: Introductionmentioning

confidence: 99%

Cytometry by time of flight identifies distinct signatures in patients with systemic sclerosis, systemic lupus erythematosus and Sjögrens syndrome

et al. 2019

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Systemic sclerosis (SSc), systemic lupus erythematosus (SLE) and primary Sjögrens syndrome (pSS) are clinically distinct systemic autoimmune diseases (SADs) that share molecular pathways. We quantified the frequency of circulating immune‐cells in 169 patients with these SADs and 44 healty controls (HC) using mass‐cytometry and assessed the diagnostic value of these results. Alterations in the frequency of immune‐cell subsets were present in all SADs compared to HC. Most alterations, including a decrease of CD56hi NK‐cells in SSc and IgM+ Bcells in pSS, were disease specific; only a reduced frequency of plasmacytoid dendritic cells was common between all SADs Strikingly, hierarchical clustering of SSc patients identified 4 clusters associated with different clinical phenotypes, and 9 of the 12 cell subset‐alterations in SSc were also present during the preclinical‐phase of the disease. Additionally, we found a strong association between the use of prednisone and alterations in B‐cell subsets. Although differences in immune‐cell frequencies between these SADs are apparent, the discriminative value thereof is too low for diagnostic purposes. Within each disease, mass cytometry analyses revealed distinct patterns between endophenotypes. Given the lack of tools enabling early diagnosis of SSc, our results justify further research into the value of cellular phenotyping as a diagnostic aid.

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“…These findings were recently replicated by van den Hoogen and colleagues, who found that approximately 50% of primary APS patients have a type I IFN signature, which was less likely to be present in patients taking either hydroxychloroquine or statins [20]**. Interestingly, they also found that the IFN signature correlated with expansion of “intermediate” and “non-classical” monocytes (which have been previously linked to cardiovascular disease in lupus and rheumatoid arthritis) [20]**. How these monocytes intersect with endothelial progenitors [42], and whether there is a role for anti-interferon therapy in APS [43], are questions that deserve further consideration.…”

Section: The Vessel Wall: Endothelial Progenitors and Interferonsmentioning

confidence: 71%

“…We found that primary APS patients have a reduction in functional endothelial progenitors, which was interestingly not dependent upon patient IgG; rather, we discovered a type I IFN signature in the APS patients, abrogation of which could restore normal progenitor function [41]*. These findings were recently replicated by van den Hoogen and colleagues, who found that approximately 50% of primary APS patients have a type I IFN signature, which was less likely to be present in patients taking either hydroxychloroquine or statins [20]**. Interestingly, they also found that the IFN signature correlated with expansion of “intermediate” and “non-classical” monocytes (which have been previously linked to cardiovascular disease in lupus and rheumatoid arthritis) [20]**.…”

Section: The Vessel Wall: Endothelial Progenitors and Interferonsmentioning

confidence: 77%

Antiphospholipid syndrome: an update for clinicians and scientists

Vreede

Bockenstedt

Knight

2017

Current Opinion in Rheumatology

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Purpose of review Antiphospholipid syndrome (APS) is a leading acquired cause of thrombosis and pregnancy loss. Upon diagnosis (which is not made until at least one morbid event has occurred), anticoagulant medications are typically prescribed in an attempt to prevent future events. This approach is not uniformly effective and does not prevent associated autoimmune and inflammatory complications. The goal of this review is to update clinicians and scientists on mechanistic and clinically-relevant studies from the past 18 months, which have especially focused on inflammatory aspects of APS pathophysiology. Recent findings How antiphospholipid antibodies leverage receptors and signaling pathways to activate cells are being increasingly defined. While established mediators of disease pathogenesis (like endothelial cells and the complement system) continue to receive intensive study, emerging concepts (such as the role of neutrophils) are also receiving increasing attention. In vivo animal studies and small clinical trials are demonstrating how repurposed medications (hydroxychloroquine, statins, rivaroxaban) may have clinical benefit in APS, with these concepts importantly supported by mechanistic data. Summary As anticoagulant medications are not uniformly effective and do not comprehensively target the underlying pathophysiology of APS, there is a continued need to reveal the inflammatory aspects of APS, which may be modulated by novel and repurposed therapies.

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Monocyte type I interferon signature in antiphospholipid syndrome is related to proinflammatory monocyte subsets, hydroxychloroquine and statin use

Cited by 51 publications

References 12 publications

Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

Activated signature of antiphospholipid syndrome neutrophils reveals potential therapeutic target

Cytometry by time of flight identifies distinct signatures in patients with systemic sclerosis, systemic lupus erythematosus and Sjögrens syndrome

Antiphospholipid syndrome: an update for clinicians and scientists

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