The chemokine receptor CCR5 Δ32 allele in natalizumab-treated multiple sclerosis

TY - JOUR

T1 - The chemokine receptor CCR5 Δ32 allele in natalizumab-treated multiple sclerosis

AU - Møller, M

AU - Søndergaard, Helle B

AU - Koch-Henriksen, N

AU - Sorensen, P S

AU - Sellebjerg, F

AU - Oturai, A B

N1 - © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

PY - 2014/1

Y1 - 2014/1

N2 - OBJECTIVE: The chemokine receptor CCR5 may be important for the recruitment of pathogenic T cells to the CNS in multiple sclerosis (MS). We hypothesized that this chemokine receptor might still be important for T-cell migration during treatment with anti-very late antigen (VLA)-4 antibody. We therefore analysed whether natalizumab-treated MS patients carrying the CCR5 Δ32 deletion allele, which results in reduced expression of CCR5 on the cell surface, had lower disease activity.METHODS: CCR5 Δ32 was analysed in 212 natalizumab-treated MS patients.RESULTS: CCR5 Δ32 status had no significant impact on the frequency of relapses 1 year prior to natalizumab treatment or during the first 48 weeks of treatment. The multiple sclerosis severity score (MSSS) was significantly lower at baseline in patients carrying CCR5 Δ32 (P = 0.031).CONCLUSIONS: CCR5 Δ32 is not associated with lower disease activity in MS patients treated with natalizumab. We found lower MSSS scores in patients carrying CCR5 Δ32 compared with the remaining patients, which is consistent with previous studies reporting an association with a more favourable disease course. Further studies are, however, needed before the relationship between CCR5 Δ32 and disease activity in MS can be definitely established.

AB - OBJECTIVE: The chemokine receptor CCR5 may be important for the recruitment of pathogenic T cells to the CNS in multiple sclerosis (MS). We hypothesized that this chemokine receptor might still be important for T-cell migration during treatment with anti-very late antigen (VLA)-4 antibody. We therefore analysed whether natalizumab-treated MS patients carrying the CCR5 Δ32 deletion allele, which results in reduced expression of CCR5 on the cell surface, had lower disease activity.METHODS: CCR5 Δ32 was analysed in 212 natalizumab-treated MS patients.RESULTS: CCR5 Δ32 status had no significant impact on the frequency of relapses 1 year prior to natalizumab treatment or during the first 48 weeks of treatment. The multiple sclerosis severity score (MSSS) was significantly lower at baseline in patients carrying CCR5 Δ32 (P = 0.031).CONCLUSIONS: CCR5 Δ32 is not associated with lower disease activity in MS patients treated with natalizumab. We found lower MSSS scores in patients carrying CCR5 Δ32 compared with the remaining patients, which is consistent with previous studies reporting an association with a more favourable disease course. Further studies are, however, needed before the relationship between CCR5 Δ32 and disease activity in MS can be definitely established.

KW - Adult

KW - Alleles

KW - Antibodies, Monoclonal, Humanized

KW - Disease Progression

KW - Female

KW - Follow-Up Studies

KW - Genotype

KW - Humans

KW - Integrin alpha4beta1

KW - Male

KW - Multiple Sclerosis, Relapsing-Remitting

KW - Prospective Studies

KW - Receptors, CCR5

KW - Sequence Deletion

KW - Severity of Illness Index

KW - Treatment Outcome

U2 - 10.1111/ane.12145

DO - 10.1111/ane.12145

M3 - Journal article

C2 - 23668375

SN - 0001-6314

VL - 129

SP - 27

EP - 31

JO - Acta Neurologica Scandinavica

JF - Acta Neurologica Scandinavica

IS - 1

ER -