Dataset Information

Variants of Novel Immunomodulatory Fc Receptor Like 5 Gene Are Associated With Multiple Sclerosis Susceptibility in the Polish Population.

ABSTRACT: Fc receptors have been shown to play a role in several autoimmune diseases. We aimed to test, for the first time, whether some of the single nucleotide variants in the FCRL5 gene were associated with multiple sclerosis (MS) susceptibility and clinical manifestations in the Polish population. The case-control study included 94 individuals with MS and 160 healthy subjects. We genotyped two single nucleotide variants of the FCRL5 gene: rs2012199 and rs6679793. The age of onset, disease duration, and clinical condition of the MS subjects were analyzed. For statistical analysis, we used the chi-squared test confirmed with Fisher's exact test. We observed the significant differences in the distribution of investigated FCRL5 genotypes between MS subjects and healthy controls. The CC and CT genotypes, as well as the C allele of rs2012199, were significantly more common in the MS subjects, as were genotypes AA and AG, and allele A of rs6679793. We noted that decreased MS susceptibility was associated with the T allele rs2012199 (OR = 0.37, p = 0.0002) and G allele rs6679793 (OR = 0.6, p = 0.02). Our results support the role of the FCRL5 locus in MS predisposition and extend the evidence of its influence on autoimmunity.

SUBMITTER: Chorazy M

PROVIDER: S-EPMC8055847 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Variants of Novel Immunomodulatory Fc Receptor Like 5 Gene Are Associated With Multiple Sclerosis Susceptibility in the Polish Population.

Chorazy Monika M Wawrusiewicz-Kurylonek Natalia N Adamska-Patruno Edyta E Czarnowska Agata A Zajkowska Olga O Kapica-Topczewska Katarzyna K Posmyk Renata R Kretowski Adam Jacek AJ Kochanowicz Jan J Kułakowska Alina A

Frontiers in neurology 20210406

Fc receptors have been shown to play a role in several autoimmune diseases. We aimed to test, for the first time, whether some of the single nucleotide variants in the <i>FCRL5</i> gene were associated with multiple sclerosis (MS) susceptibility and clinical manifestations in the Polish population. The case-control study included 94 individuals with MS and 160 healthy subjects. We genotyped two single nucleotide variants of the <i>FCRL5</i> gene: rs2012199 and rs6679793. The age of onset, diseas ...[more]

PMID: 33889124

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Project description:Nogo receptor 1 is the high affinity receptor for the potent myelin-associated inhibitory factors that make up part of the inflammatory extracellular milieu during experimental autoimmune encephalomyelitis. Signalling through the Nogo receptor 1 complex has been shown to be associated with axonal degeneration in an animal model of multiple sclerosis, and neuronal deletion of this receptor homologue, in a disease specific manner, is associated with preserving axons even in the context of neuroinflammation. The local delivery of Nogo receptor(1-310)-Fc, a therapeutic fusion protein, has been successfully applied as a treatment in animal models of spinal cord injury and glaucoma. As multiple sclerosis and experimental autoimmune encephalomyelitis exhibit large numbers of inflammatory cell infiltrates within the CNS lesions, we utilized transplantable haematopoietic stem cells as a cellular delivery method of the Nogo receptor(1-310)-Fc fusion protein. We identified CNS-infiltrating macrophages as the predominant immune-positive cell type that overexpressed myc-tagged Nogo receptor(1-310)-Fc fusion protein at the peak stage of experimental autoimmune encephalomyelitis. These differentiated phagocytes were predominant during the extensive demyelination and axonal damage, which are associated with the engulfment of the protein complex of Nogo receptor(1-310)-Fc binding to myelin ligands. Importantly, mice transplanted with haematopoietic stem cells transduced with the lentiviral vector carrying Nogo receptor(1-310)-Fc and recovered from the peak of neurological decline during experimental autoimmune encephalomyelitis, exhibiting axonal regeneration and eventual remyelination in the white matter tracts. There were no immunomodulatory effects of the transplanted, genetically modified haematopoietic stem cells on immune cell lineages of recipient female mice induced with experimental autoimmune encephalomyelitis. We propose that cellular delivery of Nogo receptor(1-310)-Fc fusion protein through genetically modified haematopoietic stem cells can modulate multifocal experimental autoimmune encephalomyelitis lesions and potentiate neurological recovery.

Dataset Information

Variants of Novel Immunomodulatory Fc Receptor Like 5 Gene Are Associated With Multiple Sclerosis Susceptibility in the Polish Population.

Publications

Variants of Novel Immunomodulatory Fc Receptor Like 5 Gene Are Associated With Multiple Sclerosis Susceptibility in the Polish Population.

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