Involvement of the choroid plexus in multiple sclerosis autoimmune inflammation: A neuropathological study

Multiple sclerosis (MS) is a severe chronic CNS disease characterized by autoimmune inflammation, demyelination, and neurodegeneration. The interaction of mitochondrial and nuclear genomes is shown to be important in the formation of a predisposition to many diseases.Objective: to analyze the association of MS with the carriage of biallelic combinations, including as components the polymorphisms of three genes of mitochondrial DNA (mtDNA) and those of 16 nuclear genes, the products of which are involved in the functioning of the immune system and may participate in the development of autoimmune inflammation in MS; and, if these combinations are identified, to determine the nature of an interaction between their components. Patients and methods. The investigation enrolled 540 MS patients and 406 control group individuals; all were Russians. The mitochondrial genome was genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. APSampler software was used for multilocus association analysis. Results and discussion. The investigators identified five biallelic combinations that were associated with MS (p=0.0036–0.022) and possessed protective properties (odds ratio (OR) 0.67–0.75). The mitochondrial component of the identified combinations was the polymorphisms m.4580 (rs28357975), m.13368 (rs3899498), and m.13708 (rs28359178) mtDNA; the nuclear component was CXCR5 (rs523604), TNFRSF1A (rs1800693), and CD86 (rs2255214) gene polymorphisms. The interaction between the components of the identified combinations was additive. Conclusion. The data obtained in the Russian population suggest that the combined contribution of the mitochondrial and nuclear genomes may affect the risk of developing MS.

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The Role of the Choroid Plexus in the Pathogenesis of Multiple Sclerosis

The Choroid Plexus and Cerebrospinal Fluid ◽

10.1016/b978-0-12-801740-1.00007-x ◽

2016 ◽

pp. 103-127 ◽

Cited By ~ 1

Author(s):

Vahan Martirosian ◽

Alex Julian ◽

Josh Neman

Keyword(s):

Multiple Sclerosis ◽

Choroid Plexus

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MIRNA 146 AND ITS ASSOCIATION WITH AUTOIMMUNE DSEASES

International Journal of Advanced Research ◽

10.21474/ijar01/12632 ◽

2021 ◽

Vol 9 (03) ◽

pp. 676-682

Author(s):

Zeinab A. Hassan ◽

◽

Ibrahim. A. Emara ◽

Sara A. Badawi ◽

Ahmed M.A. Akabawy ◽

...

Keyword(s):

Diabetes Mellitus ◽

Multiple Sclerosis ◽

Target Genes ◽

Type I Diabetes ◽

Type I Diabetes Mellitus ◽

Transcriptional Level ◽

Type I ◽

Rna Molecules ◽

Autoimmune Inflammation ◽

Immune Imbalance

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level through base-pairing predominantly with a 3-untranslated region of target mRNA, followed by mRNA degradation or translational repression. Totally, miRNAs change, through a complex regulatory network, the expression of more than 60% of human genes. MiRNAs are key regulators of the immune response that affect maturation, proliferation, differentiation, and activation of immune cells, as well as antibody secretion and release of inflammatory mediators. In this review, we generally discuss miRNAs, its types and its role in the regulation of the immune system and the autoimmune inflammatory process, focusing on the participation of miRNA-146 in the development of multiple sclerosis (MS), Rhumatoid arthritis and Type-I diabetes mellitus. Disruption of this regulation may lead to the development of various pathological conditions, including autoimmune inflammation. Special attention is given to the role of miRNA-146 in the autoimmune inflammation in multiple sclerosis, Rhumatoid arthritis and Type-I diabetes mellitus. This study concluded that, dysregulation of miR-146 and its target genes was one of the main causes for many autoimmune diseases our findings indicate a significant association of decreased miR-146 expression and the sustained immune imbalance in multiple sclerosis, Rhumatoid arthritis and Type-I diabetes mellitus.

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Correction to: Inflammation of the choroid plexus in progressive multiple sclerosis: accumulation of granulocytes and T cells

Acta Neuropathologica Communications ◽

10.1186/s40478-020-00899-5 ◽

2020 ◽

Vol 8 (1) ◽

Author(s):

Sabela Rodríguez-Lorenzo ◽

Julia Konings ◽

Susanne van der Pol ◽

Alwin Kamermans ◽

Sandra Amor ◽

...

Keyword(s):

Multiple Sclerosis ◽

T Cells ◽

Choroid Plexus ◽

Progressive Multiple Sclerosis

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Translational value of choroid plexus imaging for tracking neuroinflammation in mice and humans

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2025000118 ◽

2021 ◽

Vol 118 (36) ◽

pp. e2025000118

Author(s):

Vinzenz Fleischer ◽

Gabriel Gonzalez-Escamilla ◽

Dumitru Ciolac ◽

Philipp Albrecht ◽

Patrick Küry ◽

...

Keyword(s):

Multiple Sclerosis ◽

Choroid Plexus ◽

Mouse Models ◽

Functional Impairment ◽

Brain Parenchyma ◽

Autoimmune Encephalomyelitis ◽

Inflammatory Conditions ◽

Brain Responses ◽

Experimental Mouse ◽

Multiple Sclerosis Patients

Neuroinflammation is a pathophysiological hallmark of multiple sclerosis and has a close mechanistic link to neurodegeneration. Although this link is potentially targetable, robust translatable models to reliably quantify and track neuroinflammation in both mice and humans are lacking. The choroid plexus (ChP) plays a pivotal role in regulating the trafficking of immune cells from the brain parenchyma into the cerebrospinal fluid (CSF) and has recently attracted attention as a key structure in the initiation of inflammatory brain responses. In a translational framework, we here address the integrity and multidimensional characteristics of the ChP under inflammatory conditions and question whether ChP volumes could act as an interspecies marker of neuroinflammation that closely interrelates with functional impairment. Therefore, we explore ChP characteristics in neuroinflammation in patients with multiple sclerosis and in two experimental mouse models, cuprizone diet-related demyelination and experimental autoimmune encephalomyelitis. We demonstrate that ChP enlargement—reconstructed from MRI—is highly associated with acute disease activity, both in the studied mouse models and in humans. A close dependency of ChP integrity and molecular signatures of neuroinflammation is shown in the performed transcriptomic analyses. Moreover, pharmacological modulation of the blood–CSF barrier with natalizumab prevents an increase of the ChP volume. ChP enlargement is strongly linked to emerging functional impairment as depicted in the mouse models and in multiple sclerosis patients. Our findings identify ChP characteristics as robust and translatable hallmarks of acute and ongoing neuroinflammatory activity in mice and humans that could serve as a promising interspecies marker for translational and reverse-translational approaches.

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