Endothelial dysfunction is associated with activation of the type i interferon system and platelets in patients with systemic lupus erythematosus

Helena Tydén*, Christian Lood, Birgitta Gullstrand, Christoffer Tandrup Nielsen, Niels H.H. Heegaard, Robin Kahn, Andreas Jönsen, Anders A. Bengtsson

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Resumé

Objectives Endothelial dysfunction may be connected to cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Type I interferons (IFNs) are central in SLE pathogenesis and are suggested to induce both endothelial dysfunction and platelet activation. In this study, we investigated the interplay between endothelial dysfunction, platelets and type I IFN in SLE. Methods We enrolled 148 patients with SLE and 79 sex-matched and age-matched healthy controls (HCs). Type I IFN activity was assessed with a reporter cell assay and platelet activation by flow cytometry. Endothelial dysfunction was assessed using surrogate markers of endothelial activation, soluble vascular cell adhesion molecule-1 (sVCAM-1) and endothelial microparticles (EMPs), and finger plethysmograph to determine Reactive Hyperaemia Index (RHI). Results In patients with SLE, type I IFN activity was associated with endothelial activation, measured by high sVCAM-1 (OR 1.68, p<0.01) and elevated EMPs (OR 1.40, p=0.03). Patients with SLE with high type I IFN activity had lower RHI than HCs (OR 2.61, p=0.04), indicating endothelial dysfunction. Deposition of complement factors on platelets, a measure of platelet activation, was seen in patients with endothelial dysfunction. High levels of sVCAM-1 were associated with increased deposition of C4d (OR 4.57, p<0.01) and C1q (OR 4.10, p=0.04) on platelets. High levels of EMPs were associated with C4d deposition on platelets (OR 3.64, p=0.03). Conclusions Endothelial dysfunction was associated with activation of platelets and the type I IFN system. We suggest that an interplay between the type I IFN system, injured endothelium and activated platelets may contribute to development of CVD in SLE.

OriginalsprogEngelsk
Artikelnummere000508
TidsskriftRMD Open
Vol/bind3
Udgave nummer2
Antal sider9
DOI
StatusUdgivet - 2017

Fingeraftryk

Vascular Cell Adhesion Molecule-1
Hyperemia
Endothelium
Flow Cytometry

Citer dette

Tydén, H., Lood, C., Gullstrand, B., Nielsen, C. T., Heegaard, N. H. H., Kahn, R., ... Bengtsson, A. A. (2017). Endothelial dysfunction is associated with activation of the type i interferon system and platelets in patients with systemic lupus erythematosus. RMD Open, 3(2), [e000508]. https://doi.org/10.1136/rmdopen-2017-000508
Tydén, Helena ; Lood, Christian ; Gullstrand, Birgitta ; Nielsen, Christoffer Tandrup ; Heegaard, Niels H.H. ; Kahn, Robin ; Jönsen, Andreas ; Bengtsson, Anders A. / Endothelial dysfunction is associated with activation of the type i interferon system and platelets in patients with systemic lupus erythematosus. I: RMD Open. 2017 ; Bind 3, Nr. 2.
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title = "Endothelial dysfunction is associated with activation of the type i interferon system and platelets in patients with systemic lupus erythematosus",
abstract = "Objectives Endothelial dysfunction may be connected to cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Type I interferons (IFNs) are central in SLE pathogenesis and are suggested to induce both endothelial dysfunction and platelet activation. In this study, we investigated the interplay between endothelial dysfunction, platelets and type I IFN in SLE. Methods We enrolled 148 patients with SLE and 79 sex-matched and age-matched healthy controls (HCs). Type I IFN activity was assessed with a reporter cell assay and platelet activation by flow cytometry. Endothelial dysfunction was assessed using surrogate markers of endothelial activation, soluble vascular cell adhesion molecule-1 (sVCAM-1) and endothelial microparticles (EMPs), and finger plethysmograph to determine Reactive Hyperaemia Index (RHI). Results In patients with SLE, type I IFN activity was associated with endothelial activation, measured by high sVCAM-1 (OR 1.68, p<0.01) and elevated EMPs (OR 1.40, p=0.03). Patients with SLE with high type I IFN activity had lower RHI than HCs (OR 2.61, p=0.04), indicating endothelial dysfunction. Deposition of complement factors on platelets, a measure of platelet activation, was seen in patients with endothelial dysfunction. High levels of sVCAM-1 were associated with increased deposition of C4d (OR 4.57, p<0.01) and C1q (OR 4.10, p=0.04) on platelets. High levels of EMPs were associated with C4d deposition on platelets (OR 3.64, p=0.03). Conclusions Endothelial dysfunction was associated with activation of platelets and the type I IFN system. We suggest that an interplay between the type I IFN system, injured endothelium and activated platelets may contribute to development of CVD in SLE.",
keywords = "cardiovascular disease, disease activity, inflammation, systemic lupus erythematosus",
author = "Helena Tyd{\'e}n and Christian Lood and Birgitta Gullstrand and Nielsen, {Christoffer Tandrup} and Heegaard, {Niels H.H.} and Robin Kahn and Andreas J{\"o}nsen and Bengtsson, {Anders A.}",
year = "2017",
doi = "10.1136/rmdopen-2017-000508",
language = "English",
volume = "3",
journal = "RMD Open",
issn = "2056-5933",
publisher = "BMJ Group",
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Tydén, H, Lood, C, Gullstrand, B, Nielsen, CT, Heegaard, NHH, Kahn, R, Jönsen, A & Bengtsson, AA 2017, 'Endothelial dysfunction is associated with activation of the type i interferon system and platelets in patients with systemic lupus erythematosus', RMD Open, bind 3, nr. 2, e000508. https://doi.org/10.1136/rmdopen-2017-000508

Endothelial dysfunction is associated with activation of the type i interferon system and platelets in patients with systemic lupus erythematosus. / Tydén, Helena; Lood, Christian; Gullstrand, Birgitta; Nielsen, Christoffer Tandrup; Heegaard, Niels H.H.; Kahn, Robin; Jönsen, Andreas; Bengtsson, Anders A.

I: RMD Open, Bind 3, Nr. 2, e000508, 2017.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Endothelial dysfunction is associated with activation of the type i interferon system and platelets in patients with systemic lupus erythematosus

AU - Tydén, Helena

AU - Lood, Christian

AU - Gullstrand, Birgitta

AU - Nielsen, Christoffer Tandrup

AU - Heegaard, Niels H.H.

AU - Kahn, Robin

AU - Jönsen, Andreas

AU - Bengtsson, Anders A.

PY - 2017

Y1 - 2017

N2 - Objectives Endothelial dysfunction may be connected to cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Type I interferons (IFNs) are central in SLE pathogenesis and are suggested to induce both endothelial dysfunction and platelet activation. In this study, we investigated the interplay between endothelial dysfunction, platelets and type I IFN in SLE. Methods We enrolled 148 patients with SLE and 79 sex-matched and age-matched healthy controls (HCs). Type I IFN activity was assessed with a reporter cell assay and platelet activation by flow cytometry. Endothelial dysfunction was assessed using surrogate markers of endothelial activation, soluble vascular cell adhesion molecule-1 (sVCAM-1) and endothelial microparticles (EMPs), and finger plethysmograph to determine Reactive Hyperaemia Index (RHI). Results In patients with SLE, type I IFN activity was associated with endothelial activation, measured by high sVCAM-1 (OR 1.68, p<0.01) and elevated EMPs (OR 1.40, p=0.03). Patients with SLE with high type I IFN activity had lower RHI than HCs (OR 2.61, p=0.04), indicating endothelial dysfunction. Deposition of complement factors on platelets, a measure of platelet activation, was seen in patients with endothelial dysfunction. High levels of sVCAM-1 were associated with increased deposition of C4d (OR 4.57, p<0.01) and C1q (OR 4.10, p=0.04) on platelets. High levels of EMPs were associated with C4d deposition on platelets (OR 3.64, p=0.03). Conclusions Endothelial dysfunction was associated with activation of platelets and the type I IFN system. We suggest that an interplay between the type I IFN system, injured endothelium and activated platelets may contribute to development of CVD in SLE.

AB - Objectives Endothelial dysfunction may be connected to cardiovascular disease (CVD) in systemic lupus erythematosus (SLE). Type I interferons (IFNs) are central in SLE pathogenesis and are suggested to induce both endothelial dysfunction and platelet activation. In this study, we investigated the interplay between endothelial dysfunction, platelets and type I IFN in SLE. Methods We enrolled 148 patients with SLE and 79 sex-matched and age-matched healthy controls (HCs). Type I IFN activity was assessed with a reporter cell assay and platelet activation by flow cytometry. Endothelial dysfunction was assessed using surrogate markers of endothelial activation, soluble vascular cell adhesion molecule-1 (sVCAM-1) and endothelial microparticles (EMPs), and finger plethysmograph to determine Reactive Hyperaemia Index (RHI). Results In patients with SLE, type I IFN activity was associated with endothelial activation, measured by high sVCAM-1 (OR 1.68, p<0.01) and elevated EMPs (OR 1.40, p=0.03). Patients with SLE with high type I IFN activity had lower RHI than HCs (OR 2.61, p=0.04), indicating endothelial dysfunction. Deposition of complement factors on platelets, a measure of platelet activation, was seen in patients with endothelial dysfunction. High levels of sVCAM-1 were associated with increased deposition of C4d (OR 4.57, p<0.01) and C1q (OR 4.10, p=0.04) on platelets. High levels of EMPs were associated with C4d deposition on platelets (OR 3.64, p=0.03). Conclusions Endothelial dysfunction was associated with activation of platelets and the type I IFN system. We suggest that an interplay between the type I IFN system, injured endothelium and activated platelets may contribute to development of CVD in SLE.

KW - cardiovascular disease

KW - disease activity

KW - inflammation

KW - systemic lupus erythematosus

U2 - 10.1136/rmdopen-2017-000508

DO - 10.1136/rmdopen-2017-000508

M3 - Journal article

VL - 3

JO - RMD Open

JF - RMD Open

SN - 2056-5933

IS - 2

M1 - e000508

ER -