Increase in CCR5 Delta32/Delta32 genotype in multiple sclerosis

Area of Science:

• Immunology
• Genetics
• Neuroscience

Background:

• Chemokines and their receptors, like CCR5, are implicated in multiple sclerosis (MS) pathogenesis by mediating immune cell trafficking into the brain.
• The CCR5 Delta32 deletion mutation results in absent functional CCR5 on cell surfaces, potentially limiting immune cell infiltration into central nervous system lesions.

Purpose of the Study:

• To investigate the association between the CCR5 Delta32 genotype and the risk and course of multiple sclerosis.
• To compare CCR5 genotype frequencies in MS patients and healthy controls.
• To examine the correlation between CCR5 genotype, RNA, and protein expression in MS patients.

Main Methods:

• Genotyping analysis of CCR5 in peripheral blood mononuclear cells from 89 MS patients and 119 controls.
• Comparison of CCR5 genotype frequencies between MS patients and controls.
• Analysis of CCR5 RNA and surface protein expression in relation to genotype in 48 MS patients and 13 controls.

Main Results:

• The CCR5 Delta32/32 genotype was significantly more frequent in MS patients (6.7%) than in controls (0.8%) (P = 0.01).
• This genotype was notably increased in primary progressive MS (11.5%, P = 0.05) compared to other MS subtypes and controls.
• CCR5 surface protein expression on CD4+ cells decreased significantly with the presence of the Delta32 allele (P = 0.004).

Conclusions:

• The CCR5 Delta32/32 genotype may represent a general risk factor for developing multiple sclerosis.
• Lack of functional CCR5 does not appear to protect against MS but might predispose individuals to a more chronic disease progression.
• The chemokine system's redundancy suggests CCR5 ligands may act through alternative receptors in the absence of functional CCR5.