CCR5Δ32 – A piece of protection in the inflammatory puzzle of multiple sclerosis susceptibility

Leucocyte infiltration and activation in the central nervous system (CNS) is an important step in the pathogenesis of multiple sclerosis (MS). The Chemokine receptor 5 (CCR5) is implicated in immune cell migration and cytokine release in the CNS, and it was demonstrated to strongly contribute to CNS...

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Bibliographic Details
Published in:	Human immunology Vol. 79; no. 8; pp. 621 - 626
Main Authors:	Troncoso, Lian Lopes, Pontillo, Alessandra, Oliveira, Enedina Maria Lobato de, Finkelszteijn, Alessandro, Schneider, Silvete, Chies, José Artur Bogo
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-08-2018
Subjects:	CCR5Δ32 Central nervous system Immunogenetics Multiple sclerosis Immunogenetics Multiple sclerosis Central nervous system CCR5Δ32 Central Nervous System
Online Access:	Get full text
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Summary:	Leucocyte infiltration and activation in the central nervous system (CNS) is an important step in the pathogenesis of multiple sclerosis (MS). The Chemokine receptor 5 (CCR5) is implicated in immune cell migration and cytokine release in the CNS, and it was demonstrated to strongly contribute to CNS inflammation and damage in several models of sterile and pathogen-mediated CNS diseases. Although the inhibition of CCR5 results in a beneficial effect in experimental models of MS, conflicting results have been found about the loss-of-function variant CCR5Δ32 (rs333) in MS patients. The aim of this study was to evaluate the association of CCR5Δ32 and MS in a Brazilian case/control cohort. 261 MS patients and 435 healthy controls were genotyped for CCR5Δ32. Allelic and genotypic frequencies were compared between patients and controls (case/control analysis), and among patients classified according to the MS clinical form (relapsing remitting versus progressive) and severity (EDSS, MSSS and progression index). The CCR5Δ32 variant frequency was statistically higher in controls as compared to patients presenting European-derived ethnic background. The variant was more frequent in progressive MS as compared to RR-MS patients, and, although not statistically significant, a higher frequency of the truncated allele was observed among patients with less severe forms of MS. These findings emphasize the potential involvement of CCR5 signaling in CNS inflammation and damage in MS. The CCR5Δ32 deletion is a protective factor against the development and progression of MS in European-derived Brazilian patients.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0198-8859 1879-1166
DOI:	10.1016/j.humimm.2018.04.015