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Open AccessFeature PaperArticle

Whole-Transcriptome Analysis in Peripheral Blood Mononuclear Cells from Patients with Lipid-Specific Oligoclonal IgM Band Characterization Reveals Two Circular RNAs and Two Linear RNAs as Biomarkers of Highly Active Disease

1
Multiple Sclerosis Group, Neurosciences Area, Biodonostia Health Research Institute, 20014 San Sebastian, Spain
2
Department of Biomedical Engineering and Sciences, Tecnun-Universidad de Navarra, Manuel de Lardizábal 15, 20018 San Sebastián, Spain
3
Spanish Network of Multiple Sclerosis, 08028 Barcelona, Spain
4
Multiple Sclerosis Group, Neurosciences Area, Biodonostia Health Research Institute, Neurology Department, Basque Health Service, 20014 San Sebastian, Spain
5
Departments of Immunology and Neurology, Multiple Sclerosis Unit, Hospital Ramon y Cajal, (IRYCIS), 28034 Madrid, Spain
6
Multiple Sclerosis Group, Neurosciences Area, Biodonostia Health Research Institute, Immunology Department, Basque Health Service, 20014 San Sebastian, Spain
*
Author to whom correspondence should be addressed.
Biomedicines 2020, 8(12), 540; https://doi.org/10.3390/biomedicines8120540
Received: 26 October 2020 / Revised: 21 November 2020 / Accepted: 23 November 2020 / Published: 26 November 2020
(This article belongs to the Special Issue Multiple Sclerosis: Diagnosis and Treatment II)
The presence of anti-myelin lipid-specific oligoclonal IgM bands (LS-OCMBs) has been defined as an accurate predictor of an aggressive evolution of multiple sclerosis. However, the detection of this biomarker is performed in cerebrospinal fluid, a quite invasive liquid biopsy. In the present study we aimed at studying the expression profile of miRNA, snoRNA, circRNA and linearRNA in peripheral blood mononuclear cells (PBMCs) from patients with lipid-specific oligoclonal IgM band characterization. We included a total of 89 MS patients, 47 with negative LS-OCMB status and 42 with positive status. Microarray (miRNA and snoRNA) and RNA-seq (circular and linear RNAs) were used to perform the profiling study in the discovery cohort and candidates were validated by RT-qPCR in the whole cohort. The biomarker potential of the candidates was evaluated by ROC curve analysis. RNA-seq and RT-qPCR validation revealed that two circular (hsa_circ_0000478 and hsa_circ_0116639) and two linear RNAs (IRF5 and MTRNR2L8) are downregulated in PBMCs from patients with positive LS-OCMBs. Finally, those RNAs show a performance of a 70% accuracy in some of the combinations. The expression of hsa_circ_0000478, hsa_circ_0116639, IRF5 and MTRNR2L8 might serve as minimally invasive biomarkers of highly active disease. View Full-Text
Keywords: multiple sclerosis; biomarkers; transcriptome; microRNAs; circular RNAs; oligoclonal bands multiple sclerosis; biomarkers; transcriptome; microRNAs; circular RNAs; oligoclonal bands
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MDPI and ACS Style

Iparraguirre, L.; Olaverri, D.; Blasco, T.; Sepúlveda, L.; Castillo-Triviño, T.; Espiño, M.; Costa-Frossard, L.; Prada, Á.; Villar, L.M.; Otaegui, D.; Muñoz-Culla, M. Whole-Transcriptome Analysis in Peripheral Blood Mononuclear Cells from Patients with Lipid-Specific Oligoclonal IgM Band Characterization Reveals Two Circular RNAs and Two Linear RNAs as Biomarkers of Highly Active Disease. Biomedicines 2020, 8, 540. https://doi.org/10.3390/biomedicines8120540

AMA Style

Iparraguirre L, Olaverri D, Blasco T, Sepúlveda L, Castillo-Triviño T, Espiño M, Costa-Frossard L, Prada Á, Villar LM, Otaegui D, Muñoz-Culla M. Whole-Transcriptome Analysis in Peripheral Blood Mononuclear Cells from Patients with Lipid-Specific Oligoclonal IgM Band Characterization Reveals Two Circular RNAs and Two Linear RNAs as Biomarkers of Highly Active Disease. Biomedicines. 2020; 8(12):540. https://doi.org/10.3390/biomedicines8120540

Chicago/Turabian Style

Iparraguirre, Leire; Olaverri, Danel; Blasco, Telmo; Sepúlveda, Lucía; Castillo-Triviño, Tamara; Espiño, Mercedes; Costa-Frossard, Lucienne; Prada, Álvaro; Villar, Luisa M.; Otaegui, David; Muñoz-Culla, Maider. 2020. "Whole-Transcriptome Analysis in Peripheral Blood Mononuclear Cells from Patients with Lipid-Specific Oligoclonal IgM Band Characterization Reveals Two Circular RNAs and Two Linear RNAs as Biomarkers of Highly Active Disease" Biomedicines 8, no. 12: 540. https://doi.org/10.3390/biomedicines8120540

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