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Whole transcriptome analysis of multiple Sclerosis patients reveals active inflammatory profile in relapsing patients and downregulation of neurological repair pathways in secondary progressive cases.

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.

journal_name

Mult Scler Relat Disord

journal_title

Multiple sclerosis and related disorders

authors

Nali LH,Olival GS,Sousa FTG,de Oliveira ACS,Montenegro H,da Silva IT,Dias-Neto E,Naya H,Spangenberg L,Penalva-de-Oliveira AC,Romano CM

doi

10.1016/j.msard.2020.102243

subject

Has Abstract

pub_date

2020-09-01 00:00:00

pages

102243

eissn

2211-0348

issn

2211-0356

pii

S2211-0348(20)30319-9

journal_volume

pub_type

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Whole transcriptome analysis of multiple Sclerosis patients reveals active inflammatory profile in relapsing patients and downregulation of neurological repair pathways in secondary progressive cases.