Next-generation sequencing identifies altered whole blood microRNAs in neuromyelitis optica spectrum disorder which may permit discrimination from multiple sclerosis

Journal of Neuroinflammation

Klemens Ruprecht⁴  Florence C. Pache⁴  Friedemann Paul¹  Judith Bellmann-Strobl¹  Benjamin Meder⁵  Sven Jarius³  René M. Gieß⁴  Katharina Wakonig⁴  Catherina Pfuhl⁴  Janina R. Behrens⁴  Ludwig Rasche⁴  Christina Backes²  Jan Haas⁵  Eckart Meese⁶  Petra Leidinger⁶  Andreas Keller² 

[1] Experimental and Clinical Research Center, Max Delbrueck Center for Molecular Medicine and Charité—Universitätsmedizin Berlin, Berlin, Germany;Clinical Bioinformatics, Saarland University, Saarbrücken, Germany;Molecular Neuroimmunology Group, Department of Neurology, University of Heidelberg, Heidelberg, Germany;Clinical and Experimental Multiple Sclerosis Research Center, Charité—Universitätsmedizin Berlin, Berlin, Germany;Internal Medicine III, Heidelberg University Hospital, Heidelberg, Germany;Human Genetics, Saarland University, Homburg, Germany

关键词: Next-generation sequencing;    Serum;    Whole blood;    Biomarker;    MicroRNAs;    Multiple sclerosis;    Neuromyelitis optica spectrum disorder;   

Others  :  1230494
DOI  :  10.1186/s12974-015-0418-1

 received in 2015-07-12, accepted in 2015-10-21,  发布年份 2015

【 摘 要 】

Background

Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS) have a similar clinical phenotype but represent distinct diseases, requiring different therapies. MicroRNAs (miRNAs) are short non-coding RNAs whose expression profiles can serve as diagnostic biomarkers and which may be involved in the pathophysiology of neuroinflammatory diseases. Here, we analyzed miRNA profiles in serum and whole blood of patients with NMOSD and clinically isolated syndrome (CIS)/relapsing-remitting MS (RRMS) as well as healthy controls by next-generation sequencing (NGS).

Methods

MiRNA expression profiles were determined by NGS in sera of patients with aquaporin-4 antibody-positive NMOSD (n = 20), CIS/RRMS (n = 20), and healthy controls (n = 20) and in whole blood of patients with NMOSD (n = 11), CIS/RRMS (n = 60), and healthy controls (n = 43). Differentially expressed miRNAs were calculated by analysis of variance and t tests. All significance values were corrected for multiple testing. Selected miRNAs were validated in whole blood of patients with NMOSD (n = 18) and CIS/RRMS (n = 19) by quantitative real-time polymerase chain reaction (qRT-PCR).

Results

None of 261 miRNAs detected in serum but 178 of 416 miRNAs detected in whole blood showed significantly different expression levels among the three groups. Pairwise comparisons revealed 115 (NMOSD vs. CIS/RRMS), 141 (NMOSD vs. healthy controls), and 44 (CIS/RRMS vs. healthy controls) miRNAs in whole blood with significantly different expression levels. qRT-PCR confirmed different expression levels in whole blood of patients with NMOSD and CIS/RRMS for 9 out of 10 exemplarily chosen miRNAs. In silico enrichment analysis demonstrated an accumulation of altered miRNAs in NMOSD in particular in CD15 ⁺cells (i.e., neutrophils and eosinophils).

Conclusions

This study identifies a set of miRNAs in whole blood, which may have the potential to discriminate NMOSD from CIS/RRMS and healthy controls. In contrast, miRNA profiles in serum do not appear to be promising diagnostic biomarkers for NMOSD. Enrichment of altered miRNAs in CD15 ⁺neutrophils and eosinophils, which were previously implicated in the pathophysiology of NMOSD, suggests that miRNAs could be involved in the regulation of these cells in NMOSD.

【 授权许可】

   
2015 Keller et al.

【 图 表 】

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