Abstract
Multiple sclerosis (MS) is a neurodegenerative disease characterized by lesions in the central nervous system (CNS). Inflammation and demyelination are the leading causes of neuronal death and brain lesions formation. The immune reactivity is believed to be essential in the neuronal damage in MS. Cytokines play important role in differentiation of Th cells and recruitment of auto-reactive B and T lymphocytes that leads to neuron demyelination and death. Several cytokines have been found to be linked with MS pathogenesis. In the present study, serum level of eight cytokines (IL-1β, IL-2, IL-4, IL-8, IL-10, IL-13, IFN-γ, and TNF-α) was analyzed in USA and Russian MS to identify predictors for the disease. Further, the model was extended to classify MS into remitting and non-remitting by including age, gender, disease duration, Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) into the cytokines datasets in Russian cohorts. The individual serum cytokines data for the USA cohort was generated by Z score percentile method using R studio, while serum cytokines of the Russian cohort were analyzed using multiplex immunoassay. Datasets were divided into training (70%) and testing (30%). These datasets were used as an input into four machine learning models (support vector machine, decision tree, random forest, and neural networks) available in R programming language. Random forest model was identified as the best model for diagnosis of MS as it performed remarkable on all the considered criteria i.e., Gini, accuracy, specificity, AUC, and sensitivity. RF model also performed best in predicting remitting and non-remitting MS. The present study suggests that the concentration of serum cytokines could be used as prognostic markers for the prediction of MS.