Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target

Liu, Rongzeng; Du, Shushu; Zhao, Lili; Jain, Sahil; Sahay, Kritika; Rizvanov, Albert A.; Lezhnyova, Vera; Хайбуллин, Т И; Martynova, Ekaterina; Khaiboullina, Svetlana; Baranwal, Manoj

doi:10.3389/fimmu.2022.996469

Cited by 51 publications

(39 citation statements)

References 346 publications

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“…Also, the study by Liu and colleagues in 2022 aimed to review the current understanding of the role of antibodies and inflammatory agents as CHI3L1 in the pathophysiology of MS, their clinical relevance, and their potential as biomarkers for the disease. It concluded that higher levels of CHI3L1 in serum were associated with more severe cognitive impairment and more disease progression [40]. Moreover, the literature suggests that glial activation, which is involved in atrophic changes of the brain and axonal loss, may negatively influence different cognitive domains (e.g., episodic memory, processing speed, executive function) in MS patients [41].…”

Section: Discussionmentioning

confidence: 99%

Chitinase-3-like 1-protein in CSF: a novel biomarker for progression in patients with multiple sclerosis

et al. 2023

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Background Chitinase -3-like 1-protein (CHI3L1) is a glycoside secreted by monocytes, microglia, and activated astrocytes. Its distribution in inflammatory lesions denotes its role in astrocytic response to modulate CNS inflammation. In multiple sclerosis (MS), CHI3L1 levels have been found to be influenced by disease severity, activity, and progression. We aimed to measure CSF level of CHI3L1 in patients with MS and correlate its level with disability measures for a possible role as a biomarker for disease progression. Methods Fifty-two MS patients (30 relapsing-remitting MS and 22 progressive MS) and thirty-five age and sex-matched healthy controls were included. They all underwent full clinical assessment (including disability and cognitive scales), radiological assessment, and CSF level of CHI3L1. Results Patients with MS had higher CSF level of CHI3L1 than controls. Patients with progressive forms had higher levels than relapsing forms. There were positive correlations between disease duration, number of attacks, total EDSS, and CSF level of CHI3L1. Patients who had higher level of CSF CHI3L1 showed worse performance in MMSE and BICAMS and more lesions in T2 MRI brain. A cut off value of 154 ng/mL was found between patients with RRMS and PMS patients. Conclusion CHI3L1 can be considered as a biomarker of disease progression. CHI3L1 level increases in progressive MS more than RRMS. Also, high CSF level of CHI3L1 was associated with more disability including motor, cognitive, and radiological aspects.

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Section: Discussionmentioning

confidence: 99%

Chitinase-3-like 1-protein in CSF: a novel biomarker for progression in patients with multiple sclerosis

et al. 2023

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“…One survey of MS lesions found CD8 + T cells and CD20 + B cells to predominate across all disease and lesion stages, while CD4 + T cells were sparse [ 131 ]. As reviewed by Liu et al, Th1 and Th17 lymphocytes appear to be the primary mediators of damage to myelin sheaths in MS, and B cells that produce autoantibodies to myelin protein have been observed in MS patients [ 132 ]. The cacophony of chemokines and cytokines that are produced during MS is most likely responsible for the recruitment of Th1 and Th17 CD4 + T cells, CD8 + T cells, and B cells that further contribute to CNS damage in MS and experimental autoimmune encephalomyelitis (EAE), an animal model for MS [ 131 , 133 , 134 , 135 ].…”

Section: Multiple Sclerosismentioning

confidence: 99%

Immune Regulatory Functions of Macrophages and Microglia in Central Nervous System Diseases

Poppell

Hammel

Ren

2023

IJMS

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Macrophages can be characterized as a very multifunctional cell type with a spectrum of phenotypes and functions being observed spatially and temporally in various disease states. Ample studies have now demonstrated a possible causal link between macrophage activation and the development of autoimmune disorders. How these cells may be contributing to the adaptive immune response and potentially perpetuating the progression of neurodegenerative diseases and neural injuries is not fully understood. Within this review, we hope to illustrate the role that macrophages and microglia play as initiators of adaptive immune response in various CNS diseases by offering evidence of: (1) the types of immune responses and the processes of antigen presentation in each disease, (2) receptors involved in macrophage/microglial phagocytosis of disease-related cell debris or molecules, and, finally, (3) the implications of macrophages/microglia on the pathogenesis of the diseases.

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“…Myelin reactive CD4+ T cells perform a key role in demyelination, after their migration into the CNS, whilst naive T lymphocytes maturation to Th1 and Th17 are another myelin specific deterioration mechanism, secreting pro-inflammatory cytokines, with antigen presentation, via major histocompatibility complex II, on dendritic cells, being the main T-cell activation mechanism [ 9 ]. B-lymphocytes could also contribute to MS pathogenesis by producing anti-myelin basic protein antibodies [ 10 ].…”

Section: Inflammation and Oxidative Stress In Msmentioning

confidence: 99%

The Multiple Sclerosis Modulatory Potential of Natural Multi-Targeting Antioxidants

Theodosis-Nobelos

Rekka

2022

Molecules

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Multiple sclerosis (MS) is a complex neurodegenerative disease. Although its pathogenesis is rather vague in some aspects, it is well known to be an inflammatory process characterized by inflammatory cytokine release and oxidative burden, resulting in demyelination and reduced remyelination and axonal survival together with microglial activation. Antioxidant compounds are gaining interest towards the manipulation of MS, since they offer, in most of the cases, many benefits, due to their pleiotropical activity, that mainly derives from the oxidative stress decrease. This review analyzes research articles, of the last decade, which describe biological in vitro, in vivo and clinical evaluation of various categories of the most therapeutically applied natural antioxidant compounds, and some of their derivatives, with anti-MS activity. It also summarizes some of the main characteristics of MS and the role the reactive oxygen and nitrogen species may have in its progression, as well as their relation with the other mechanistic aspects of the disease, in order for the multi-targeting potential of those antioxidants to be defined and the source of origination of such activity explained. Antioxidant compounds with specific characteristics are expected to affect positively some aspects of the disease, and their potential may render them as effective candidates for neurological impairment reduction in combination with the MS treatment regimen. However, more studies are needed in order such antioxidants to be established as recommended treatment to MS patients.

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Autoreactive lymphocytes in multiple sclerosis: Pathogenesis and treatment target

Cited by 51 publications

References 346 publications

Chitinase-3-like 1-protein in CSF: a novel biomarker for progression in patients with multiple sclerosis

Chitinase-3-like 1-protein in CSF: a novel biomarker for progression in patients with multiple sclerosis

Immune Regulatory Functions of Macrophages and Microglia in Central Nervous System Diseases

The Multiple Sclerosis Modulatory Potential of Natural Multi-Targeting Antioxidants

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