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Genetic, Immune-Inflammatory, and Oxidative Stress Biomarkers as Predictors for Disability and Disease Progression in Multiple Sclerosis

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Abstract

The aim of this study was to evaluate the TNFβ NcoI polymorphism (rs909253) and immune-inflammatory, oxidative, and nitrosative stress (IO&NS) biomarkers as predictors of disease progression in multiple sclerosis (MS). We included 212 MS patients (150 female, 62 male, mean (±standard deviation (SD)) age = 42.7 ± 13.8 years) and 249 healthy controls (177 female, 72 male, 36.8 ± 11 years). The disability was measured the Expanded Disability Status Scale (EDSS) in 2006 and 2011. We determined the TNFβ NcoI polymorphism and serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-4, IL-10, and IL-17, albumin, ferritin, and plasma levels of lipid hydroperoxides (CL-LOOH), carbonyl protein, advanced oxidation protein products (AOPPs), nitric oxide metabolites (NOx), and total radical-trapping antioxidant parameter (TRAP). The mean EDSS (±SD) in 2006 was 1.62 ± 2.01 and in 2011 3.16 ± 2.29, and disease duration was 7.34 ± 7.0 years. IL-10, TNF-α, IFN-γ, AOPP, and NOx levels were significantly higher and IL-4 lower in MS patients with a higher 2011 EDSS scores (≥3) as compared with those with EDSS < 3. The actual increases in EDSS from 2006 to 2011 were positively associated with TNF-α and IFN-γ. Increased IFN-γ values were associated with higher pyramidal symptoms and increased IL-6 with sensitive symptoms. Increased carbonyl protein and IL-10 but lowered albumin levels predicted cerebellar symptoms. The TNFB1/B2 genotype decreased risk towards progression of pyramidal symptoms. Treatments with IFN-β and glatiramer acetate significantly reduced TNF-α but did not affect the other IO&NS biomarkers or disease progression. Taken together, IO&NS biomarkers and NcoI TNFβ genotypes predict high disability in MS and are associated with different aspects of disease progression. New drugs to treat MS should also target oxidative stress pathways.

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Acknowledgments

The study was 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); State University of Londrina (PROPPG). We thank the University Hospital of State University of Londrina and HUTec Foundation for technical and administrative supports.

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Authors and Affiliations

  1. Health Sciences Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, 86.038-440, Brazil

    Ana Paula Kallaur, Sayonara Rangel Oliveira, Wildea Lice de Carvalho Jennings Pereira, Daniela Frizon Alfieri & Tamires Flauzino

  2. Department of Pathology, Clinical Analysis and Toxicology, Health Sciences Center, State University of Londrina, Av. Robert Koch, 60, Londrina, Paraná, CEP 86.038-440, Brazil

    Edna Maria Vissoci Reiche, Andrea Name Colado Simão & Marcell Alysson Batisti Lozovoy

  3. Outpatient Clinic for Demyelinating Diseases, University Hospital, State University of Londrina, Londrina, Paraná, 86061-335, Brazil

    Wildea Lice de Carvalho Jennings Pereira, Caio de Meleck Proença & Damacio Ramón Kaimen-Maciel

  4. Department of Clinical Medicine, Health Sciences Center, State University of Londrina, Londrina, Paraná, 86.038-440, Brazil

    Damacio Ramón Kaimen-Maciel

  5. Impact Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia

    Michael Maes

  6. Department of Psychiatry, King Chulalongkorn Memorial Hospital, Chulalongkorn, Bangkok, Thailand

    Michael Maes

Authors
  1. Ana Paula Kallaur
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  2. Edna Maria Vissoci Reiche
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  3. Sayonara Rangel Oliveira
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  4. Andrea Name Colado Simão
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  5. Wildea Lice de Carvalho Jennings Pereira
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  6. Daniela Frizon Alfieri
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  7. Tamires Flauzino
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  8. Caio de Meleck Proença
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  9. Marcell Alysson Batisti Lozovoy
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  10. Damacio Ramón Kaimen-Maciel
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  11. Michael Maes
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Corresponding author

Correspondence to Edna Maria Vissoci Reiche.

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Kallaur, A.P., Reiche, E.M.V., Oliveira, S.R. et al. Genetic, Immune-Inflammatory, and Oxidative Stress Biomarkers as Predictors for Disability and Disease Progression in Multiple Sclerosis. Mol Neurobiol 54, 31–44 (2017). https://doi.org/10.1007/s12035-015-9648-6

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  • DOI: https://doi.org/10.1007/s12035-015-9648-6

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