Original article| Volume 44, 102243, September 2020

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

  • Luiz H. Nali
    Laboratório de Virologia, Instituto de Medicina Tropical de São Paulo, LIM-52 (LIMHC) Universidade de São Paulo, Rua Dr. Enéas de Carvalho Aguiar, 470, São Paulo, 05403-000, Brazil.

    Post-graduation Program in Health Sciences, Santo Amaro University, Rua Prof. Enéas de Siqueira Neto, 340, São Paulo, 04829-300, Brazil
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  • Guilherme S. Olival
    Departamento de Neurologia Santa Casa de Misericórdia de São Paulo, R. Dr. Cesário Mota Júnior, 112, São Paulo, 01221-020 Brazil
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  • Francielle T.G. Sousa
    Laboratório de Virologia, Instituto de Medicina Tropical de São Paulo, LIM-52 (LIMHC) Universidade de São Paulo, Rua Dr. Enéas de Carvalho Aguiar, 470, São Paulo, 05403-000, Brazil.
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  • Ana Carolina S. de Oliveira
    Laboratório de Virologia, Instituto de Medicina Tropical de São Paulo, LIM-52 (LIMHC) Universidade de São Paulo, Rua Dr. Enéas de Carvalho Aguiar, 470, São Paulo, 05403-000, Brazil.
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  • Horácio Montenegro
    Departamento de Zootecnia, ESALQ/USP, Piracicaba, SP 13400-183,Brazil
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  • Israel T. da Silva
    Laboratory of Medical Genomics, A.C.Camargo Cancer Center, São Paulo, 01525-001, Brazil
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  • Emamnuel Dias-Neto
    Laboratory of Medical Genomics, A.C.Camargo Cancer Center, São Paulo, 01525-001, Brazil

    Laboratory of Neurosciences (LIM-27), Institute of Psychiatry, São Paulo Medical School, University of São Paulo, São Paulo, Brazil
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  • Hugo Naya
    Unidad de Bioinformática Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, 11400, Uruguay
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  • Lucia Spangenberg
    Unidad de Bioinformática Institut Pasteur de Montevideo, Mataojo 2020, Montevideo, 11400, Uruguay
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  • Augusto C. Penalva-de-Oliveira
    Departamento de Neurologia Santa Casa de Misericórdia de São Paulo, R. Dr. Cesário Mota Júnior, 112, São Paulo, 01221-020 Brazil

    Departamento de Neurologia, Instituto de Infectologia Emilio Ribas, Avenida Doutor Arnaldo, 165, São Paulo, 01246-900, Brazil
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  • Camila M. Romano
    Corresponding author at: Hospital das Clinicas HCFMUSP (LIM52), Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
    Laboratório de Virologia, Instituto de Medicina Tropical de São Paulo, LIM-52 (LIMHC) Universidade de São Paulo, Rua Dr. Enéas de Carvalho Aguiar, 470, São Paulo, 05403-000, Brazil.

    Hospital das Clinicas HCFMUSP (LIM52), Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil
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      • 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.



      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.


      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.


      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.


      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.


      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.


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