Highlights
- •More than 1.000 genes were differentially expressed in MS patients.
- •RRMS and SPMS presents distinct patterns of gene expression.
- •SPMS gene profile are consistently linked to a neurodegenerative profile.
- •RRMS transcriptomic profile presents several upregulated proinflammatory pathways.
- •RERE, IRS2, SIPA1L1, TANC2 and PLAGL1 genes are upregulated in both RRMS and SPMS.
Abstract
Background
Multiple sclerosis (MS) is an inflammatory autoimmune neurologic disease that causes
progressive destruction of myelin sheath and axons. Affecting more than 2 million
people worldwide, MS may presents distinct clinical courses. However, information
regarding key gene expression and genic pathways related to each clinical form is
still limited.
Objective
To assess the whole transcriptome of blood leukocytes from patients with remittent-recurrent
(RRMS) and secondary-progressive (SPMS) forms to explore the gene expression profile
of each form.
Methods
Total RNA was obtained and sequenced in Illumina HiSeq platform. Reads were aligned
to human genome (GRCh38/hg38), BAM files were mapped and differential expression was
obtained with DeSeq2. Up or downregulated pathways were obtained through Ingenuity
IPA. Pro-inflammatory cytokines levels were also assessed.
Results
The transcriptome was generated for nine patients (6 SPMS and 3 RRMS) and 5 healthy
controls. A total of 731 and 435 differentially expressed genes were identified in
SPMS and RRMS, respectively. RERE, IRS2, SIPA1L1, TANC2 and PLAGL1 were upregulated in both forms, whereas PAD2 and PAD4 were upregulated in RRMS and downregulated in SPMS. Inflammatory and neuronal repair
pathways were upregulated in RRMS, which was also observed in cytokine analysis. Conversely,
SPMS patients presented IL-8, IL-1, Neurothrophin and Neuregulin pathways down regulated.
Conclusions
Overall, the transcriptome of RRMS and SPMS clearly indicated distinct inflammatory profiles,
where RRMS presented marked pro-inflammatory profile but SPMS did not. SPMS individuals
also presented a decrease on expression of neuronal repair pathways.
Keywords
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Article info
Publication history
Published online: June 03, 2020
Accepted:
May 25,
2020
Received in revised form:
April 21,
2020
Received:
January 20,
2020
Identification
Copyright
© 2020 Elsevier B.V. All rights reserved.
