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

Journal: Metabolic brain disease
PMID:

Abstract

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.

Authors

  • Tamires Flauzino
    Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil.
  • Andrea Name Colado Simão
    Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Parana, Brazil.
  • Wildea Lice de Carvalho Jennings Pereira
    Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil.
  • Daniela Frizon Alfieri
    Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Parana, Brazil.
  • Sayonara Rangel Oliveira
    Department of Pathology, Clinical Analysis and Toxicology, Health Sciences Center, University Hospital, State University of Londrina, Av. Robert Koch 60, Londrina, Paraná, CEP 86038-350, Brazil.
  • Ana Paula Kallaur
    Postgraduate Program, Health Sciences Center, State University of Londrina, Londrina, Paraná, Brazil.
  • Marcell Alysson Batisti Lozovoy
    Department of Pathology, Clinical Analysis and Toxicology, University of Londrina, Londrina, Parana, Brazil.
  • Damacio Ramón Kaimen-Maciel
    Department of Clinical Medicine, University of Londrina, Londrina, Paraná, Brazil.
  • Michael Maes
    Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • Edna Maria Vissoci Reiche
    Department of Pathology, Clinical Analysis and Toxicology, Health Sciences Center, University Hospital, State University of Londrina, Av. Robert Koch 60, Londrina, Paraná, CEP 86038-350, Brazil. reiche@sercomtel.com.br.