Disability in multiple sclerosis is associated with age and inflammatory, metabolic and oxidative/nitrosative stress biomarkers: results of multivariate and machine learning procedures

  • Tamires Flauzino
  • Andrea Name Colado Simão
  • Wildea Lice de Carvalho Jennings Pereira
  • Daniela Frizon Alfieri
  • Sayonara Rangel Oliveira
  • Ana Paula Kallaur
  • Marcell Alysson Batisti Lozovoy
  • Damacio Ramón Kaimen-Maciel
  • Michael Maes
  • Edna Maria Vissoci ReicheEmail author
Original Article


The aim of this study was to evaluate the immune-inflammatory, metabolic, and nitro-oxidative stress (IM&NO) biomarkers as predictors of disability in multiple sclerosis (MS) patients. A total of 122 patients with MS were included; their disability was evaluated using the Expanded Disability Status Scale (EDSS) and IM&NO biomarkers were evaluated in peripheral blood samples. Patients with EDSS ≥3 were older and showed higher homocysteine, uric acid, advanced oxidized protein products (AOPP) and low-density lipoprotein (LDL)-cholesterol and higher rate of metabolic syndrome (MetS), while high-density lipoprotein (HDL)-cholesterol was lower than in patients with EDSS <3; 84.6% of all patients were correctly classified in these EDSS subgroups. We found that 36.3% of the variance in EDSS score was explained by age, Th17/T regulatory (Treg) and LDL/HDL ratios and homocysteine (all positively related) and body mass index (BMI) (inversely related). After adjusting for MS treatment modalities, the effects of the LDL/HDL and zTh17/Treg ratios, homocysteine and age on disability remained, whilst BMI was no longer significant. Moreover, carbonyl proteins were associated with increased disability. In conclusion, the results showed that an inflammatory Th17 profile coupled with age and increased carbonyl proteins were the most important variables associated with high disability followed at a distance by homocysteine, MetS and LDL/HDL ratio. These data underscore that IM&NO pathways play a key role in increased disability in MS patient and may be possible new targets for the treatment of these patients. Moreover, a panel of these laboratory biomarkers may be used to predict the disability in MS.


Multiple sclerosis Disability Inflammation Oxidative stress Homocysteine Biomarkers 


Author’s contributions

Conception and research design: Edna Maria Vissoci Reiche and Andrea Name Colado Simão; Manuscript writing and discussion of results: Edna Maria Vissoci Reiche, Andrea Name Colado Simão; Tamires Flauzino; Data collection: Damacio Ramón Kaimen-Maciel, Wildea Lice de Carvalho Jennings Pereira, Tamires Flauzino, Daniela Frizon Alfieri, Ana Paula Kallaur, and Sayonara Rangel Oliveira, which contributed equally; Laboratory analysis: Tamires Flauzino, Daniela Frizon Alfieri, Marcell Alysson Batisti Lozovoy; Statistical analysis: Andrea Name Colado Simão, Michael Maes. All authors have read and approved the final manuscript.

Financial support

This study was partially and financially supported by Novartis Biosciences S.A for the development of the research according to the Researcher’s Initiative Study CFTY720DBR07T. The authors do not receive any reimbursement or financial benefits and declare that they have no competing interests. Novartis Biosciences S.A. played no role in the design, methods, data management or analysis or in the decision to publish. The study was also supported by grants from Coordination for the Improvement of Higher Level of Education Personnel (CAPES) of Brazilian Ministry of Education; Institutional Program for Scientific Initiation Scholarship (PIBIC) of the National Council for Scientific and Technological Development (CNPq).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The protocol was approved by the Institutional Research Ethics Committees of University of Londrina, Paraná, Brazil (CAAE: 22290913.9.0000.5231) and all of the individuals invited were informed in detail about the research and gave written Informed Consent.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Tamires Flauzino
    • 1
  • Andrea Name Colado Simão
    • 2
  • Wildea Lice de Carvalho Jennings Pereira
    • 1
  • Daniela Frizon Alfieri
    • 1
  • Sayonara Rangel Oliveira
    • 2
  • Ana Paula Kallaur
    • 1
  • Marcell Alysson Batisti Lozovoy
    • 2
  • Damacio Ramón Kaimen-Maciel
    • 3
  • Michael Maes
    • 4
    • 5
  • Edna Maria Vissoci Reiche
    • 2
    Email author
  1. 1.Postgraduate Program, Health Sciences CenterState University of LondrinaLondrinaBrazil
  2. 2.Department of Pathology, Clinical Analysis and Toxicology, Health Sciences CenterUniversity Hospital, State University of LondrinaLondrinaBrazil
  3. 3.Department of Clinical MedicineUniversity of LondrinaLondrinaBrazil
  4. 4.Impact Strategic Research Centre, School of MedicineDeakin UniversityGeelongAustralia
  5. 5.Department of PsychiatryKing Chulalongkorn Memorial HospitalBangkokThailand

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