Expression of chemokine receptors in the different clinical forms of multiple sclerosis

2002 ◽  
Vol 8 (5) ◽  
pp. 390-395 ◽  
Author(s):  
E M Martínez-Cáceres ◽  
C Espejo ◽  
L Brieva ◽  
I Pericot ◽  
M Tintoré ◽  
...  

Chemokines and their receptors are important in the trafficking of peripheral leukocytes into the central nervous system, a major event in the pathogenesis of multiple sclerosis (MS). Evidence based on clinical, pathological and magnetic resonance imaging grounds supports some divergence between forms of MS with relapses [relapsing-remitting (RR) and secondary progressive (SP)] and the primary progressive (PP) form. To elucidate whether different pathogenic mechanisms are involved in PPMS, we compared membrane expression of a group of CC and CXC chemokine receptors (CCR1, CCR5, CXCR3, CXCR4) in peripheral blood of 68 MS patients (25 PPMS, 23 SPMS and 20 RRMS) and 26 healthy controls. We found a significant increase in surface expression of CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients compared to controls. Increased levels of CXCL10 (IP-10) and CCL5 (RANTES) in cerebrospinal fluid were also observed in a subgroup of MS patients. These results support that chemokines and their receptors are involved in the pathogenesis of MS. However, a pattern of chemokine-chemokine receptor expression characteristic of each clinical form of the disease failed to be observed.

2019 ◽  
Vol 28 (12) ◽  
pp. 1507-1527 ◽  
Author(s):  
Giovanni Schepici ◽  
Serena Silvestro ◽  
Placido Bramanti ◽  
Emanuela Mazzon

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating, and degenerative disease that affects the central nervous system. A recent study showed that interaction between the immune system and the gut microbiota plays a crucial role in the development of MS. This review reports the clinical studies carried out in recent years that aimed to evaluate the composition of the microbiota in patients with relapsing–remitting MS (RR-MS). We also report what is available in the literature regarding the effectiveness of fecal microbiota transplantation and the role of the diet in restoring the intestinal bacterial population. Studies report that patients with RR-MS have a microbiota that, compared with healthy controls, has higher amounts of Pedobacteria, Flavobacterium, Pseudomonas, Mycoplana, Acinetobacter, Eggerthella, Dorea, Blautia, Streptococcus and Akkermansia. In contrast, MS patients have a microbiota with impoverished microbial populations of Prevotella, Bacteroides, Parabacteroides, Haemophilus, Sutterella, Adlercreutzia, Coprobacillus, Lactobacillus, Clostridium, Anaerostipes and Faecalibacterium. In conclusion, the restoration of the microbial population in patients with RR-MS appears to reduce inflammatory events and the reactivation of the immune system.


Author(s):  
Nora Fitri ◽  
Basjiruddin Ahmad ◽  
Yuliarni Syafrita

Multiple sclerosis (MS) is the most common neurologic demyelinating disease in high-income countries. The causes of MS is multifactorial involve genetics and the environment in which immune cell infiltration occurs across the blood-brain barrier, causing inflammation, demyelination, gliosis, and neuroaxonal degeneration in the substantia grisea in the central nervous system. A 23-year-old female patient was treated with four limbs weakened since 2 weeks ago accompanied by blurred vision, pain, cramps and stiffness in the back muscles and legs. The patient has experienced the same complaint before. Clinical findings reveal lhermitte sign, atrophy papillae, and tetraparese. On thoracic vertebral MRI examination without contrast and brain MRI with contrast obtained multiple sclerosis lesions. Patients receive steroid and antidepressant therapy. MS needs to be studied further because this number of cases began to emerge. 


2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199957
Author(s):  
Fernando Labella ◽  
Fernando Acebrón ◽  
María del Carmen Blanco-Valero ◽  
Alba Rodrígez-Martín ◽  
Ángela Monterde Ortega ◽  
...  

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system whose etiology remains unclear. It has been suggested that MS can be triggered by certain viruses; however, human immunodeficiency virus (HIV) infection is associated with reduced incidence of MS. We present the case of a young patient diagnosed with active relapsing-remitting MS whose clinical course substantially improved following HIV infection and treatment. The patient achieved no evidence of disease activity status without any disease-modifying drugs. Both HIV-induced immunosuppression and antiretroviral therapy may have attenuated the clinical course in this patient.


Author(s):  
M Hoseinipourasl ◽  
M Zandkarimi ◽  
J Abdolmohammadi ◽  
K Sharifi ◽  
S Miraki

Background: Multiple sclerosis (MS) is a chronic, typically progressive and most common autoimmune disease which damaged the central nervous system. According to the reports in 2008, this disorder has affected 2 and 2.5 million people globally. While the reason is not clear, proposed causes for this include immunologic, environmental, infectious and genetic factors, and sexuality. MS can cause many symptoms, including blurred vision, loss of balance, poor coordination, slurred speech, tremors, numbness, extreme fatigue, problems with memory and concentration, paralysis, blindness, and more. There are four distinguished illness fields in MS: relapsing-remitting MS (RRMS), primary–progressive MS (PPMS), secondary–progressive MS (SPMS), and progressive–relapsing. MRI is a great tool to identify the asymptomatic distribution of lesions in space and time.Materials and Methods: 32 patients with MS plaques were evaluated by FLAIR and DWI pre- and post-Gadolinium injection compared with 15minutes delay T1w SE.Results: FLAIR post-inject had significantly better detection of the number and signal intensity of active MS lesions. DWI and ADC images detected active plaques different from non-active lesions without contrast.Conclusion: The result of this study showed that FLAIR post-inject had the highest sensitivity in detection of active MS lesions due to the CSF signal suppression in FLAIR, thus offering enough TR time recovery in active enhanced plaques.


2020 ◽  
Vol 21 (23) ◽  
pp. 9249
Author(s):  
Lars Masanneck ◽  
Susann Eichler ◽  
Anna Vogelsang ◽  
Melanie Korsen ◽  
Heinz Wiendl ◽  
...  

Cyclic GMP-AMP-synthase is a sensor of endogenous nucleic acids, which subsequently elicits a stimulator of interferon genes (STING)-dependent type I interferon (IFN) response defending us against viruses and other intracellular pathogens. This pathway can drive pathological inflammation, as documented for type I interferonopathies. In contrast, specific STING activation and subsequent IFN-β release have shown beneficial effects on experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Although less severe cases of relapse-remitting MS (RRMS) are treated with IFN-β, there is little information correlating aberrant type I IFN signaling and the pathologic conditions of MS. We hypothesized that there is a link between STING activation and the endogenous production of IFN-β during neuroinflammation. Gene expression analysis in EAE mice showed that Sting level decreased in the peripheral lymphoid tissue, while its level increased within the central nervous system over the course of the disease. Similar patterns could be verified in peripheral immune cells during the acute phases of RRMS in comparison to remitting phases and appropriately matched healthy controls. Our study is the first to provide evidence that the STING/IFN-β-axis is downregulated in RRMS patients, meriting further intensified research to understand its role in the pathophysiology of MS and potential translational applications.


2020 ◽  
Vol 12 (3) ◽  
pp. 89-108
Author(s):  
Grace Lassiter ◽  
Carlie Melancon ◽  
Tyler Rooney ◽  
Anne-Marie Murat ◽  
Jessica S. Kaye ◽  
...  

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing–remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.


2020 ◽  
Vol 9 (5) ◽  
pp. 1468
Author(s):  
Zbyšek Pavelek ◽  
Francesco Angelucci ◽  
Ondřej Souček ◽  
Jan Krejsek ◽  
Lukáš Sobíšek ◽  
...  

Background: Multiple sclerosis (MS) is a neurodegenerative disease that affects the central nervous system. The cause of MS is still unknown, and the role of innate immunity is still poorly understood. Objective: The goal of this study was to understand whether, compared to healthy controls, the elements of innate immunity are altered in the blood of MS patients in the remitting phase. Methods: A total of 77 naïve MS patients and 50 healthy controls were included in this cohort study. Peripheral blood samples were collected and analyzed. All the calculations were performed with the statistical system R (r-project.org). Results: The results showed that MS patients had significantly lower relative representations of granulocytes than healthy controls, while the relative representations of monocytes remained unchanged. CD64- and PD-L1-positive granulocytes exhibited a nonsignificant decreasing trend, while granulocytes with other membrane markers remained noticeably unchanged. Conclusion: The results of this study suggest that studies of the causes of MS and its treatment should also be focused on the elements of the innate immune response.


2013 ◽  
Vol 19 (12) ◽  
pp. 1673-1675 ◽  
Author(s):  
JWL Brown ◽  
AJ Coles ◽  
JL Jones

Balo’s concentric sclerosis (BCS) is a rare demyelinating disorder of the central nervous system. The humanised monoclonal antibody alemtuzumab has shown efficacy in another demyelinating disorder, relapsing–remitting multiple sclerosis. We aimed to explore its efficacy in treatment-refractory BCS. A 52-year-old male with radiologically confirmed progressive BCS resistant to steroids, plasmapharesis and cyclophosphamide was administered a standard protocol of alemtuzumab. Treatment failed to slow his decline; he died 6 months after administration. Why alemtuzumab induced no clinical or radiological impact may be multifactorial. We review the evidence directing BCS therapy and propose the next steps for exploring this potentially fatal condition.


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