Proteolipid Protein Gene Expression in Demyelination and Remyelination of the Central Nervous System: A Model for Multiple Sclerosis

1994 ◽  
Vol 53 (2) ◽  
pp. 136-143 ◽  
Author(s):  
Moses Rodriguez ◽  
Naraporn Prayoonwiwat ◽  
Charles Howe ◽  
Kathleen Sanborn
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Protein Gene ◽  
Proteolipid Protein ◽  
System A ◽  
The Central Nervous System

scholarly journals Initiation and Exacerbation of Autoimmune Demyelination of the Central Nervous System via Virus-Induced Molecular Mimicry: Implications for the Pathogenesis of Multiple Sclerosis

2005 ◽  
Vol 79 (13) ◽  
pp. 8581-8590 ◽  
Author(s):  
J. Ludovic Croxford ◽  
Julie K. Olson ◽  
Holly A. Anger ◽  
Stephen D. Miller
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Demyelinating Disease ◽  
Molecular Mimicry ◽  
Proteolipid Protein ◽  
Rapid Onset ◽  
Epidemiological Studies ◽  
The Central Nervous System ◽  
Disease Initiation

ABSTRACT Epidemiological studies indicate that infectious agents are important in the pathogenesis of multiple sclerosis (MS). Our previous reports showed that the infection of SJL mice with a nonpathogenic variant of Theiler's murine encephalomyelitis virus (TMEV) engineered to express a naturally occurring Haemophilus influenzae-encoded molecular mimic (HI574-586) of an immunodominant self-myelin proteolipid protein epitope (PLP139-151) induced a rapid-onset demyelinating disease associated with the activation of PLP139-151-specific Th1 responses. The current results extend our previous findings in four critical respects. We show that disease initiation by the H. influenzae mimic is prevented by tolerance to the self PLP139-151 epitope, definitively proving the occurrence of infection-induced molecular mimicry. We demonstrate that the H. influenzae mimic epitope can be processed from the flanking sequences within the native mimic protein. We show that the H. influenzae mimic epitope only induces an immunopathologic self-reactive Th1 response and subsequent clinical disease in the context of the TMEV infection and not when administered in complete Freund's adjuvant, indicating that molecular mimicry-induced disease initiation requires virus-activated innate immune signals. Lastly, we show that the infection of SJL mice with TMEV expressing the H. influenzae mimic can exacerbate a previously established nonprogressive autoimmune disease of the central nervous system. Collectively, these findings illustrate the evolving mechanisms by which virus infections may contribute to both the initiation and exacerbation of autoimmune diseases, and they have important implications for MS pathogenesis.

scholarly journals Differential Gene Expression Patterns in Blood and Cerebrospinal Fluid of Multiple Sclerosis and Neuro-Behçet Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Olfa Maghrebi ◽  
Mariem Hanachi ◽  
Khadija Bahrini ◽  
Mariem Kchaou ◽  
Cyrine Jeridi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Cerebrospinal Fluid ◽  
Nervous System ◽  
Neurological Disorders ◽  
Expression Patterns ◽  
Behçet Disease ◽  
Behcet Disease ◽  
The Central Nervous System

Inflammatory demyelinating disorders of the central nervous system are debilitating conditions of the young adult, here we focus on multiple sclerosis (MS) and neuro-Behçet disease (NBD). MS is an autoimmune disorder of the central nervous system. NBD, a neurological manifestation of an idiopathic chronic relapsing multisystem inflammatory disease, the behçet disease. The diagnosis of MS and NBD relies on clinical symptoms, magnetic resonance imaging and laboratory tests. At first onset, clinical and imaging similarities between the two disorders may occur, making differential diagnosis challenging and delaying appropriate management. Aiming to identify additional discriminating biomarker patterns, we measured and compared gene expression of a broad panel of selected genes in blood and cerebrospinal fluid (CSF) cells of patients suffering from NBD, MS and non inflammatory neurological disorders (NIND). To reach this aim, bivariate and multivariate analysis were applied. The Principal Analysis Component (PCA) highlighted distinct profiles between NBD, MS, and controls. Transcription factors foxp3 in the blood along with IL-4, IL-10, and IL-17 expressions were the parameters that are the main contributor to the segregation between MS and NBD clustering. Moreover, parameters related to cellular activation and inflammatory cytokines within the CSF clearly differentiate between the two inflammatory diseases and the controls. We proceeded to ROC analysis in order to identify the most distinctive parameters between both inflammatory neurological disorders. The latter analysis suggested that IL-17, CD73 in the blood as well as IL-1β and IL-10 in the CSF were the most discriminating parameters between MS and NBD. We conclude that combined multi-dimensional analysis in blood and CSF suggests distinct mechanisms governing the pathophysiology of these two neuro-inflammatory disorders.

Sign in / Sign up

Export Citation Format

Share Document