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• W1898841705 abstract "Chemokines and their receptors participate in the development of multiple sclerosis (MS) by guiding immune cells into the brain tissue. A CCR5 Δ32 deletion mutation abolishes functional CCR5 on the cell surface and may reduce cell entry into the lesion sites. To analyse the significance of this mutation in MS, we compared the frequencies of CCR5 genotype in peripheral blood mononuclear cells from 89 MS patients and 119 healthy controls. The CCR5 genotype was further compared with the CCR5 RNA and surface protein expression in 48 MS patients and their controls. In all MS patients, the Δ32/32 genotype was found with 6.7% frequency, whereas it was present only in 0.8% of the controls (6/89 vs 1/119, P = 0.01). Specifically, the Δ32/Δ32 genotype was increased (11.5%, P = 0.05) among primary progressive MS patients, whereas it was present only in 4.8% in other MS subtypes and only in 0.8% of the controls. The amount of CCR5 protein on CD4+ cells analysed in 48 MS patients (nine primary progressive MS, 18 secondary progressive MS, 21 relapsing–remitting MS) and 13 controls decreased with genotype, being 8.9% in wt/wt, 7.7% in wt/Δ32 and 4.3% in Δ32/Δ32. CCR5 surface expression analysed on these 48 MS patients and 13 controls was significantly decreased in Δ32/Δ32 MS patients as compared with that in wt/wt genotype individuals (P = 0.004). The significantly increased number of Δ32/Δ32 individuals among our MS patients suggests that this genotype could contribute as a general risk factor for MS. However, neither the levels of RNA or surface protein correlated with MS subtype, neurological disability as expressed by expanded disability status scale, or disease progression index. Our results suggest that the lack of CCR5 does not protect from MS, but rather it may predispose to the chronic course of the disease. This would further imply that in view of the redundancy in the chemokine system, CCR5 ligands must be assumed to function through other closely related chemokine receptors." @default.
• W1898841705 created "2016-06-24" @default.
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• W1898841705 date "2004-05-01" @default.
• W1898841705 modified "2023-10-17" @default.
• W1898841705 title "Increase in CCR5 Delta32/Delta32 genotype in multiple sclerosis" @default.
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• W1898841705 doi "https://doi.org/10.1046/j.1600-0404.2003.00233.x" @default.
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