Blood platelet RNA enables the detection of multiple sclerosis

Nik Sol; Cyra E Leurs; Sjors Gjg In 't Veld; Eva M Strijbis; Adrienne Vancura; Markus W Schweiger; Charlotte E Teunissen; Farrah J Mateen; Bakhos A Tannous; Myron G Best; Thomas Würdinger; Joep Killestein; Sjors GJG In ’t Veld

doi:https://doi.org/10.1177/2055217320946784

Blood platelet RNA enables the detection of multiple sclerosis

Nik Sol, Cyra E Leurs, Sjors Gjg In 't Veld, Eva M Strijbis, Adrienne Vancura, Markus W Schweiger, Charlotte E Teunissen, Farrah J Mateen, Bakhos A Tannous, Myron G Best, Thomas Würdinger, Joep Killestein, Sjors GJG In ’t Veld

Research output: Contribution to journal › Article › Academic › peer-review

13 Citations (Scopus)

Abstract

Background: In multiple sclerosis (MS), clinical assessment, MRI and cerebrospinal fluid are important in the diagnostic process. However, no blood biomarker has been confirmed as a useful tool in the diagnostic work-up.

Objectives: Blood platelets contain a rich spliced mRNA repertoire that can alter during megakaryocyte development but also during platelet formation and platelet circulation. In this proof of concept study, we evaluate the diagnostic potential of spliced blood platelet RNA for the detection of MS.

Methods: We isolated and sequenced platelet RNA of blood samples obtained from 57 MS patients and 66 age- and gender-matched healthy controls (HCs). 60% was used to develop a particle swarm-optimized (PSO) support vector machine classification algorithm. The remaining 40% served as an independent validation series.

Results: In total, 1249 RNAs with differential spliced junction expression levels were identified between platelets of MS patients as compared to HCs, including EPSTI1, IFI6, and RPS6KA3, in line with reported inflammatory signatures in the blood of MS patients. The RNAs were subsequently used as input for a MS classifier, capable of detecting MS with 80% accuracy in the independent validation series.

Conclusions: Spliced platelet RNA may enable the blood-based diagnosis of MS, warranting large-scale validation.

Original language	English
Pages (from-to)	2055217320946784
Journal	Multiple sclerosis journal - experimental, translational and clinical
Volume	6
Issue number	3
DOIs	https://doi.org/10.1177/2055217320946784
Publication status	Published - 28 Aug 2020

Keywords

Multiple sclerosis
RNA
biomarker
diagnostics
platelets

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https://doi.org/10.1177/2055217320946784

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Sol, N., Leurs, C. E., Veld, S. G. I. ., Strijbis, E. M., Vancura, A., Schweiger, M. W., Teunissen, C. E., Mateen, F. J., Tannous, B. A., Best, M. G., Würdinger, T., Killestein, J., & Veld, S. GJG. I. . (2020). Blood platelet RNA enables the detection of multiple sclerosis. Multiple sclerosis journal - experimental, translational and clinical, 6(3), 2055217320946784. https://doi.org/10.1177/2055217320946784

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title = "Blood platelet RNA enables the detection of multiple sclerosis",

abstract = "Background: In multiple sclerosis (MS), clinical assessment, MRI and cerebrospinal fluid are important in the diagnostic process. However, no blood biomarker has been confirmed as a useful tool in the diagnostic work-up.Objectives: Blood platelets contain a rich spliced mRNA repertoire that can alter during megakaryocyte development but also during platelet formation and platelet circulation. In this proof of concept study, we evaluate the diagnostic potential of spliced blood platelet RNA for the detection of MS.Methods: We isolated and sequenced platelet RNA of blood samples obtained from 57 MS patients and 66 age- and gender-matched healthy controls (HCs). 60% was used to develop a particle swarm-optimized (PSO) support vector machine classification algorithm. The remaining 40% served as an independent validation series.Results: In total, 1249 RNAs with differential spliced junction expression levels were identified between platelets of MS patients as compared to HCs, including EPSTI1, IFI6, and RPS6KA3, in line with reported inflammatory signatures in the blood of MS patients. The RNAs were subsequently used as input for a MS classifier, capable of detecting MS with 80% accuracy in the independent validation series.Conclusions: Spliced platelet RNA may enable the blood-based diagnosis of MS, warranting large-scale validation.",

keywords = "Multiple sclerosis, RNA, biomarker, diagnostics, platelets",

author = "Nik Sol and Leurs, {Cyra E} and Veld, {Sjors Gjg In 't} and Strijbis, {Eva M} and Adrienne Vancura and Schweiger, {Markus W} and Teunissen, {Charlotte E} and Mateen, {Farrah J} and Tannous, {Bakhos A} and Best, {Myron G} and Thomas W{\"u}rdinger and Joep Killestein and Veld, {Sjors GJG In {\textquoteright}t}",

note = "{\textcopyright} The Author(s) 2020.",

year = "2020",

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day = "28",

doi = "https://doi.org/10.1177/2055217320946784",

language = "English",

volume = "6",

pages = "2055217320946784",

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Sol, N , Leurs, CE, Veld, SGI, Strijbis, EM, Vancura, A, Schweiger, MW , Teunissen, CE, Mateen, FJ, Tannous, BA, Best, MG , Würdinger, T , Killestein, J & Veld, SGJGI 2020, 'Blood platelet RNA enables the detection of multiple sclerosis', Multiple sclerosis journal - experimental, translational and clinical, vol. 6, no. 3, pp. 2055217320946784. https://doi.org/10.1177/2055217320946784

TY - JOUR

T1 - Blood platelet RNA enables the detection of multiple sclerosis

AU - Sol, Nik

AU - Leurs, Cyra E

AU - Veld, Sjors Gjg In 't

AU - Strijbis, Eva M

AU - Vancura, Adrienne

AU - Schweiger, Markus W

AU - Teunissen, Charlotte E

AU - Mateen, Farrah J

AU - Tannous, Bakhos A

AU - Best, Myron G

AU - Würdinger, Thomas

AU - Killestein, Joep

AU - Veld, Sjors GJG In ’t

PY - 2020/8/28

Y1 - 2020/8/28

N2 - Background: In multiple sclerosis (MS), clinical assessment, MRI and cerebrospinal fluid are important in the diagnostic process. However, no blood biomarker has been confirmed as a useful tool in the diagnostic work-up.Objectives: Blood platelets contain a rich spliced mRNA repertoire that can alter during megakaryocyte development but also during platelet formation and platelet circulation. In this proof of concept study, we evaluate the diagnostic potential of spliced blood platelet RNA for the detection of MS.Methods: We isolated and sequenced platelet RNA of blood samples obtained from 57 MS patients and 66 age- and gender-matched healthy controls (HCs). 60% was used to develop a particle swarm-optimized (PSO) support vector machine classification algorithm. The remaining 40% served as an independent validation series.Results: In total, 1249 RNAs with differential spliced junction expression levels were identified between platelets of MS patients as compared to HCs, including EPSTI1, IFI6, and RPS6KA3, in line with reported inflammatory signatures in the blood of MS patients. The RNAs were subsequently used as input for a MS classifier, capable of detecting MS with 80% accuracy in the independent validation series.Conclusions: Spliced platelet RNA may enable the blood-based diagnosis of MS, warranting large-scale validation.

AB - Background: In multiple sclerosis (MS), clinical assessment, MRI and cerebrospinal fluid are important in the diagnostic process. However, no blood biomarker has been confirmed as a useful tool in the diagnostic work-up.Objectives: Blood platelets contain a rich spliced mRNA repertoire that can alter during megakaryocyte development but also during platelet formation and platelet circulation. In this proof of concept study, we evaluate the diagnostic potential of spliced blood platelet RNA for the detection of MS.Methods: We isolated and sequenced platelet RNA of blood samples obtained from 57 MS patients and 66 age- and gender-matched healthy controls (HCs). 60% was used to develop a particle swarm-optimized (PSO) support vector machine classification algorithm. The remaining 40% served as an independent validation series.Results: In total, 1249 RNAs with differential spliced junction expression levels were identified between platelets of MS patients as compared to HCs, including EPSTI1, IFI6, and RPS6KA3, in line with reported inflammatory signatures in the blood of MS patients. The RNAs were subsequently used as input for a MS classifier, capable of detecting MS with 80% accuracy in the independent validation series.Conclusions: Spliced platelet RNA may enable the blood-based diagnosis of MS, warranting large-scale validation.

KW - Multiple sclerosis

KW - RNA

KW - biomarker

KW - diagnostics

KW - platelets

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U2 - https://doi.org/10.1177/2055217320946784

DO - https://doi.org/10.1177/2055217320946784

M3 - Article

C2 - 32843989

SN - 2055-2173

VL - 6

SP - 2055217320946784

JO - Multiple sclerosis journal - experimental, translational and clinical

JF - Multiple sclerosis journal - experimental, translational and clinical

IS - 3

ER -

Blood platelet RNA enables the detection of multiple sclerosis

Abstract

Keywords

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