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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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Nali, Luiz H. [1, 2] ; Olival, Guilherme S. [3] ; Sousa, Francielle T. G. [1] ; de Oliveira, Ana Carolina S. [1] ; Montenegro, Horacio [4] ; da Silva, Israel T. [5] ; Dias-Neto, Emamnuel [5, 6] ; Naya, Hugo ; Spangenberg, Lucia [7] ; Penalva-de-Oliveira, Augusto C. [8] ; Romano, Camila M. [9, 1]
Total Authors: 11
Affiliation:
[1] Univ Sao Paulo, Lab Virol, Inst Medicina Trop Sao Paulo, LIM52 LIMHC, Rua Dr Eneas de Carvalho Aguiar, BR-05403000 Sao Paulo - Brazil
[2] Univ Santo Amaro, Postgraduat Program Hlth Sci, Rua Prof Eneas Siqueira Neto 340, BR-04829300 Sao Paulo - Brazil
[3] Dept Neurol Santa Casa Misericordia Sao Paulo, R Dr Cesario Mota Jr 112, BR-01221020 Sao Paulo - Brazil
[4] ESALQ USP, Dept Zootecnia, BR-13400183 Piracicaba, SP - Brazil
[5] AC Camargo Canc Ctr, Lab Med Genom, BR-01525001 Sao Paulo - Brazil
[6] Univ Sao Paulo, Sao Paulo Med Sch, Inst Psychiat, Lab Neurosci LIM 27, Sao Paulo - Brazil
[7] Unidad Bioinformat Inst Pasteur Montevideo, Mataojo 2020, Montevideo 11400 - Uruguay
[8] Inst Infectol Emilio Ribas, Dept Neurol, Ave Doutor Arnaldo 165, BR-01246900 Sao Paulo - Brazil
[9] Univ Sao Paulo, Fac Med, Hosp Clin HCFMUSP LIM52, Sao Paulo - Brazil
Total Affiliations: 9
Document type: Journal article
Source: MULTIPLE SCLEROSIS AND RELATED DISORDERS; v. 44, SEP 2020.
Web of Science Citations: 0
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. (AU)

FAPESP's process: 13/24223-9 - Expression profile of Human endogenous retrovirus W (HERV-W)in individuals with Multiples Sclerosis under relapsing conditions
Grantee:Luiz Henrique da Silva Nali
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 15/05958-3 - The role of the Human Endogenous Retrovirus Family W (HERV-W) activity in the pathogenesis of multiple sclerosis investigated by transcriptome analysis of patients affected
Grantee:Camila Malta Romano
Support Opportunities: Regular Research Grants