Abstract
BackgroundIn 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.ObjectivesBlood 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.MethodsWe 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.ResultsIn 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.ConclusionsSpliced platelet RNA may enable the blood-based diagnosis of MS, warranting large-scale validation.
Highlights
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder affecting the central nervous system
Platelet collection Blood was collected from healthy controls (HCs) (n 1⁄4 66) and multiple sclerosis (MS) patients (n 1⁄4 57) in EDTA-coated Vacutainer tubes
P value 0.70 0.91 blood draw, the disability status of MS patients was examined according to the Kurtzke Expanded Disability Status Scale (EDSS) and an magnetic resonance imaging (MRI) scan was acquired
Summary
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disorder affecting the central nervous system. During the final stages of thrombopoiesis, platelets are loaded with pre-mature messenger RNAs (pre-mRNAs) before being released from the megakaryocyte.[3] As a result, platelets contain a rich RNA repertoire that can change during megakaryocyte development and during platelet formation and platelet circulation (Figure 1(a)). In multiple sclerosis (MS), clinical assessment, MRI and cerebrospinal fluid are important in the diagnostic process. Objectives: Blood platelets contain a rich spliced mRNA repertoire that can alter during megakaryocyte development and 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. Conclusions: Spliced platelet RNA may enable the blood-based diagnosis of MS, warranting large-scale validation
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