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Elevated plasma homocysteine levels are associated with disability progression in patients with multiple sclerosis

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Abstract

The aims of this study were to verify whether hyperhomocysteinemia is associated with disability progression in Multiple Sclerosis (MS) patients and whether TNF pathways and cellular adhesion molecules (CAM) are involved in this process. This study included 180 MS patients, who were divided according to their levels of homocysteine (Hyperhomocysteinemia ≥11.35 μmol/L) and 204 healthy individuals (control group). MS patients showed higher levels of homocysteine (p < 0.001), tumor necrosis factor alpha (TNF-α, p < 0.001), TNF receptor 1 (TNFR1, p = 0.038), TNF receptor 2 (TNFR2, p < 0.001), and lower levels of PECAM (p = 0.001), ICAM (p < 0.001) and VCAM (p = 0.005) than controls. The multivariate binary logistic regression analysis showed that plasma levels of homocysteine, TNFR1, TNFR2 and PECAM were associated with the presence of disease. MS patients with hyperhomocysteinemia showed higher disease progression evaluated by the Multiple Sclerosis Severity Score (MSSS, p < 0.001), disability evaluated by Expanded Disability Status Score EDSS (p < 0.001), TNFR1 (p = 0.039) and ICAM (p = 0.034) than MS patients with lower levels of homocysteine. Hyperhomocysteinemia was independently associated with MSSS in MS patients, but were not associated with TNF-α, TNFR, and CAM. Homocysteine levels was higher in progressive forms than relapsing-remitting MS (p < 0.001), independently of sex and age. In conclusion, this is the first study in which homocysteinemia was associated with progression of the disease (MSSS), although this finding was not directly related to TNF-α and TNFR pathways or to CAM.

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Authors and Affiliations

  1. Department of Pathology, Clinical Analysis and Toxicology, Health Sciences Center, University Hospital, State University of Londrina, Av. Robert Koch 60, Vila Operária, Londrina, Paraná, CEP 86038-350, Brazil

    Sayonara Rangel Oliveira, Helena Kaminami Morimoto, Elaine Regina Delicato de Almeida, Marcell Alysson Batisti Lozovoy, Edna Maria Vissoci Reiche & Andréa Name Colado Simão

  2. Postgraduate Program, Health Sciences Center, University of Londrina, Londrina, Paraná, Brazil

    Tamires Flauzino, Ana Paula Kallaur & Daniela Frizon Alfieri

  3. Applied Immunology Laboratory, University of Londrina, Londrina, Paraná, Brazil

    Beatriz Sardinha Sabino

  4. Department of Clinical Medicine, University of Londrina, Londrina, Paraná, Brazil

    Damacio Ramon Kaimen-Maciel

  5. Department of Internal Medicine, University of Londrina, Londrina, Paraná, Brazil

    Isaias Dichi

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  1. Sayonara Rangel Oliveira
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  2. Tamires Flauzino
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  3. Beatriz Sardinha Sabino
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  4. Ana Paula Kallaur
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  5. Daniela Frizon Alfieri
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  6. Damacio Ramon Kaimen-Maciel
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  7. Helena Kaminami Morimoto
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  8. Elaine Regina Delicato de Almeida
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  9. Marcell Alysson Batisti Lozovoy
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  11. Isaias Dichi
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  12. Andréa Name Colado Simão
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Correspondence to Andréa Name Colado Simão.

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Oliveira, S.R., Flauzino, T., Sabino, B.S. et al. Elevated plasma homocysteine levels are associated with disability progression in patients with multiple sclerosis. Metab Brain Dis 33, 1393–1399 (2018). https://doi.org/10.1007/s11011-018-0224-4

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  • DOI: https://doi.org/10.1007/s11011-018-0224-4

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