Cerebrospinal fluid cells immune landscape in multiple sclerosis

Abstract

Background Multiple Sclerosis (MS) is a potentially devastating autoimmune neurological disorder, which characteristically induces demyelination of white matter in the brain and spinal cord. Methods In this study, three characteristics of the central nervous system (CNS) immune microenvironment occurring during MS onset were explored; immune cell proportion alteration, differential gene expression profile, and related pathways. The raw data of two independent datasets were obtained from the ArrayExpress database; E-MTAB-69, which was used as a derivation cohort, and E-MTAB-2374 which was used as a validation cohort. Differentially expressed genes (DEGs) were identified by the false discovery rate (FDR) value of < 0.05 and |log2 (Fold Change)|> 1, for further analysis. Then, functional enrichment analyses were performed to explore the pathways associated with MS onset. The gene expression profiles were analyzed using CIBERSORT to identify the immune type alterations involved in MS disease. Results After verification, the proportion of five types of immune cells (plasma cells, monocytes, macrophage M2, neutrophils and eosinophils) in cerebrospinal fluid (CSF) were revealed to be significantly altered in MS cases compared to the control group. Thus, the complement and coagulation cascades and the systemic lupus erythematosus (SLE) pathways may play critical roles in MS. We identified NLRP3, LILRB2, C1QB, CD86, C1QA, CSF1R, IL1B and TLR2 as eight core genes correlated with MS. Conclusions Our study identified the change in the CNS immune microenvironment of MS cases by analysis of the in silico data using CIBERSORT. Our data may assist in providing directions for further research as to the molecular mechanisms of MS and provide future potential therapeutic targets in treatment.

Multi-parametric MRI phenotype with trustworthy machine learning for differentiating CNS demyelinating diseases

“…The accuracy of clinical visual analysis in our study complied with the studies [ 38 – 42 ] with the reported accuracy ranging from 0.573 to 0.739. In this study, doctors misdiagnosed about 25% of patients with MS as NMO, similar to the previous study [ 2 ], which justified the machine learning model provide valuable assistance for clinical decisions. Remarkably, the multi-parametric phenotype demonstrated the highest discriminative ability (AUC 0.902 ± 0.027) in the independent testing, outperforming the discriminative performance of the T2 (AUC 0.852), T1-MPRAGE (AUC 0.880) and clinical phenotypes (AUC 0.573).…”

“…Multiple sclerosis (MS) and Neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system (CNS), which are the most common causes of neurological disability in young people [ 1 ]. In the pathogenesis of these two diseases, a variety of immune-related molecules and pathways are different [ 2 ]. In clinical practice, the differential diagnosis of these two diseases is still challenging.…”

Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease

“…Additionally, we observed that complement and coagulation cascade pathway may play a critical role in DM-ILD. This pathway has been reported in immune diseases, such as multiple sclerosis ( Li et al, 2021 ), Ig A nephropathy, and Henoch–Schönlein purpura nephritis ( Fang et al, 2021 ). Complement activation has been demonstrated in previous reports ( Roy et al, 2020 ; Tripathi et al, 2021 ) to be associated with type I interferon, which was significantly activated in DM and DM-ILD ( Zhang et al, 2019a ; de Jesus et al, 2020 ).…”

Research Progress of Artificial Intelligence Image Analysis in Systemic Disease-Related Ophthalmopathy

“…Neuromyelitis optica (NMO) and multiple sclerosis (MS) are demyelinating diseases of the central nervous system and are the most common causes of neurological dysfunction in young and middle-aged people [32]. The pathogenesis of MS and NMO is mainly related to various immune-related molecules and immune pathways [33]. NMO mainly selectively involves the optic nerve and spinal cord, and the main clinical manifestations are rapid and severe visual loss in both eyes at the same time or in succession, such as optic disk edema, tortuous dilatation of retinal veins, perioptic exudation, and other fundus changes; recovery of visual function is poor, and most patients suffer from serious visual impairment in both eyes or at least one eye.…”