Associations of circulating cell-free microRNA with vasculopathy and vascular events in systemic lupus erythematosus patients

S. Kay*, A. Carlsen, A. Voss, M. Burton, ACP Diederichsen, M. K. Poulsen, NHH Heegaard

*Kontaktforfatter for dette arbejde

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a high risk of atherosclerosis and cardiovascular disease (CVD). MicroRNAs (miRNAs) are small non-coding RNAs that modulate protein translation, and dysregulation is seen in autoimmunity, atherosclerosis, and CVD. We investigate associations between circulating miRNAs and markers of atherosclerosis in SLE patients. Method: A group (n = 121) of well-characterized SLE patients were screened for atherosclerosis by cardiac computed tomography and carotid ultrasound. RNA was purified from plasma and 46 specific miRNAs were determined using quantitative real-time polymerase chain reaction. Results: Forty-one miRNAs were consistently detected. Fifty out of 118 available SLE patients had atherosclerosis. A profile consisting of three miRNAs (decreased miR-125b, miR-101, miR-375) was indicative of atherosclerosis. Multivariate logistic regression identified eight clinical manifestations associated with atherosclerotic outcome. The full classification profile showed a specificity of 88% and a sensitivity of 86%. Hierarchical clustering identified an eight-miRNA profile that differentiated a subgroup of SLE patients (n = 16) who had significantly increased venous thrombotic events (p = 0.045), a higher prevalence of β2-glycoprotein I antibodies (p = 0.029), and an increased prevalence of thrombocytopenia (p = 0.028). Conclusion: In this cross-sectional study, the circulating miRNA profile distinguished SLE patients with atherosclerosis from those without. Furthermore, an eight-miRNA signature was associated with thrombocytopenia, venous thrombotic events, and β2-glycoprotein I antibodies in SLE patients. Prospective studies are needed to confirm the findings and to establish the precise role of circulating miRNA profiling in the evaluation of atherosclerosis in SLE.

OriginalsprogEngelsk
TidsskriftScandinavian Journal of Rheumatology
Vol/bind48
Udgave nummer1
Sider (fra-til)32-41
ISSN0300-9742
DOI
StatusUdgivet - jan. 2019

Fingeraftryk

MicroRNAs
Autoimmunity
Cluster Analysis
Real-Time Polymerase Chain Reaction
Cross-Sectional Studies
Logistic Models
Prospective Studies
RNA

Citer dette

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title = "Associations of circulating cell-free microRNA with vasculopathy and vascular events in systemic lupus erythematosus patients",
abstract = "Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a high risk of atherosclerosis and cardiovascular disease (CVD). MicroRNAs (miRNAs) are small non-coding RNAs that modulate protein translation, and dysregulation is seen in autoimmunity, atherosclerosis, and CVD. We investigate associations between circulating miRNAs and markers of atherosclerosis in SLE patients. Method: A group (n = 121) of well-characterized SLE patients were screened for atherosclerosis by cardiac computed tomography and carotid ultrasound. RNA was purified from plasma and 46 specific miRNAs were determined using quantitative real-time polymerase chain reaction. Results: Forty-one miRNAs were consistently detected. Fifty out of 118 available SLE patients had atherosclerosis. A profile consisting of three miRNAs (decreased miR-125b, miR-101, miR-375) was indicative of atherosclerosis. Multivariate logistic regression identified eight clinical manifestations associated with atherosclerotic outcome. The full classification profile showed a specificity of 88{\%} and a sensitivity of 86{\%}. Hierarchical clustering identified an eight-miRNA profile that differentiated a subgroup of SLE patients (n = 16) who had significantly increased venous thrombotic events (p = 0.045), a higher prevalence of β2-glycoprotein I antibodies (p = 0.029), and an increased prevalence of thrombocytopenia (p = 0.028). Conclusion: In this cross-sectional study, the circulating miRNA profile distinguished SLE patients with atherosclerosis from those without. Furthermore, an eight-miRNA signature was associated with thrombocytopenia, venous thrombotic events, and β2-glycoprotein I antibodies in SLE patients. Prospective studies are needed to confirm the findings and to establish the precise role of circulating miRNA profiling in the evaluation of atherosclerosis in SLE.",
author = "S. Kay and A. Carlsen and A. Voss and M. Burton and ACP Diederichsen and Poulsen, {M. K.} and NHH Heegaard",
year = "2019",
month = "1",
doi = "10.1080/03009742.2018.1450892",
language = "English",
volume = "48",
pages = "32--41",
journal = "Scandinavian Journal of Rheumatology",
issn = "0300-9742",
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Associations of circulating cell-free microRNA with vasculopathy and vascular events in systemic lupus erythematosus patients. / Kay, S.; Carlsen, A.; Voss, A.; Burton, M.; Diederichsen, ACP; Poulsen, M. K.; Heegaard, NHH.

I: Scandinavian Journal of Rheumatology, Bind 48, Nr. 1, 01.2019, s. 32-41.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Associations of circulating cell-free microRNA with vasculopathy and vascular events in systemic lupus erythematosus patients

AU - Kay, S.

AU - Carlsen, A.

AU - Voss, A.

AU - Burton, M.

AU - Diederichsen, ACP

AU - Poulsen, M. K.

AU - Heegaard, NHH

PY - 2019/1

Y1 - 2019/1

N2 - Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a high risk of atherosclerosis and cardiovascular disease (CVD). MicroRNAs (miRNAs) are small non-coding RNAs that modulate protein translation, and dysregulation is seen in autoimmunity, atherosclerosis, and CVD. We investigate associations between circulating miRNAs and markers of atherosclerosis in SLE patients. Method: A group (n = 121) of well-characterized SLE patients were screened for atherosclerosis by cardiac computed tomography and carotid ultrasound. RNA was purified from plasma and 46 specific miRNAs were determined using quantitative real-time polymerase chain reaction. Results: Forty-one miRNAs were consistently detected. Fifty out of 118 available SLE patients had atherosclerosis. A profile consisting of three miRNAs (decreased miR-125b, miR-101, miR-375) was indicative of atherosclerosis. Multivariate logistic regression identified eight clinical manifestations associated with atherosclerotic outcome. The full classification profile showed a specificity of 88% and a sensitivity of 86%. Hierarchical clustering identified an eight-miRNA profile that differentiated a subgroup of SLE patients (n = 16) who had significantly increased venous thrombotic events (p = 0.045), a higher prevalence of β2-glycoprotein I antibodies (p = 0.029), and an increased prevalence of thrombocytopenia (p = 0.028). Conclusion: In this cross-sectional study, the circulating miRNA profile distinguished SLE patients with atherosclerosis from those without. Furthermore, an eight-miRNA signature was associated with thrombocytopenia, venous thrombotic events, and β2-glycoprotein I antibodies in SLE patients. Prospective studies are needed to confirm the findings and to establish the precise role of circulating miRNA profiling in the evaluation of atherosclerosis in SLE.

AB - Objective: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with a high risk of atherosclerosis and cardiovascular disease (CVD). MicroRNAs (miRNAs) are small non-coding RNAs that modulate protein translation, and dysregulation is seen in autoimmunity, atherosclerosis, and CVD. We investigate associations between circulating miRNAs and markers of atherosclerosis in SLE patients. Method: A group (n = 121) of well-characterized SLE patients were screened for atherosclerosis by cardiac computed tomography and carotid ultrasound. RNA was purified from plasma and 46 specific miRNAs were determined using quantitative real-time polymerase chain reaction. Results: Forty-one miRNAs were consistently detected. Fifty out of 118 available SLE patients had atherosclerosis. A profile consisting of three miRNAs (decreased miR-125b, miR-101, miR-375) was indicative of atherosclerosis. Multivariate logistic regression identified eight clinical manifestations associated with atherosclerotic outcome. The full classification profile showed a specificity of 88% and a sensitivity of 86%. Hierarchical clustering identified an eight-miRNA profile that differentiated a subgroup of SLE patients (n = 16) who had significantly increased venous thrombotic events (p = 0.045), a higher prevalence of β2-glycoprotein I antibodies (p = 0.029), and an increased prevalence of thrombocytopenia (p = 0.028). Conclusion: In this cross-sectional study, the circulating miRNA profile distinguished SLE patients with atherosclerosis from those without. Furthermore, an eight-miRNA signature was associated with thrombocytopenia, venous thrombotic events, and β2-glycoprotein I antibodies in SLE patients. Prospective studies are needed to confirm the findings and to establish the precise role of circulating miRNA profiling in the evaluation of atherosclerosis in SLE.

U2 - 10.1080/03009742.2018.1450892

DO - 10.1080/03009742.2018.1450892

M3 - Journal article

VL - 48

SP - 32

EP - 41

JO - Scandinavian Journal of Rheumatology

JF - Scandinavian Journal of Rheumatology

SN - 0300-9742

IS - 1

ER -