CCL5 and CCR5 genotypes modify clinical, radiological and pathological features of multiple sclerosis

Tineke van Veen, Jessica Nielsen, Johannes Berkhof, Frederik Barkhof, Wouter Kamphorst, Lars Bö, Rivka Ravid, Cor L. Verweij, Inge Huitinga, Chris H. Polman, Bernard M.J. Uitdehaag

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Chemokines mediate selective recruitment of leukocyte subsets into the CNS during inflammatory episodes. We hypothesised that functional polymorphisms in CCR5 and CCL5 influence perivascular leukocyte infiltration, inflammation, axonal loss, and remyelination, and disease course. Therefore, we determined genotypes at four possibly functional polymorphisms in CCR5 and CCL5 for 637 patients and 92 brain donors with multiple sclerosis (MS). For a subset of 192 patients, MRI data were available. We found that low-producer allele CCL5-403*G was associated with reduced risk of severe axonal loss, whereas high-producer allele CCL5-403*A was associated with a worse clinical disease course measured by the MS Functional Composite Score and MS Severity Score. Low-producer allele CCR5 + 303*G was associated with reduced T2 hyperintense and T1 hypointense lesion volumes on MRI, and high-producer allele CCR5 + 303*A with early age at onset. Furthermore, low-producer allele CCR5Δ32 was associated with reduced T2 lesion volume, lower black hole ratio on MRI, and with a higher percentage of lesions with signs of remyelination, histopathologically. In summary, our multifaceted study supports the notion that polymorphisms in CCL5 and CCR5 modify the course of MS.

Original languageEnglish
Pages (from-to)157-164
Number of pages8
JournalJournal of Neuroimmunology
Volume190
Issue number1-2
DOIs
Publication statusPublished - 1 Oct 2007

Cite this

van Veen, Tineke ; Nielsen, Jessica ; Berkhof, Johannes ; Barkhof, Frederik ; Kamphorst, Wouter ; Bö, Lars ; Ravid, Rivka ; Verweij, Cor L. ; Huitinga, Inge ; Polman, Chris H. ; Uitdehaag, Bernard M.J. / CCL5 and CCR5 genotypes modify clinical, radiological and pathological features of multiple sclerosis. In: Journal of Neuroimmunology. 2007 ; Vol. 190, No. 1-2. pp. 157-164.
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abstract = "Chemokines mediate selective recruitment of leukocyte subsets into the CNS during inflammatory episodes. We hypothesised that functional polymorphisms in CCR5 and CCL5 influence perivascular leukocyte infiltration, inflammation, axonal loss, and remyelination, and disease course. Therefore, we determined genotypes at four possibly functional polymorphisms in CCR5 and CCL5 for 637 patients and 92 brain donors with multiple sclerosis (MS). For a subset of 192 patients, MRI data were available. We found that low-producer allele CCL5-403*G was associated with reduced risk of severe axonal loss, whereas high-producer allele CCL5-403*A was associated with a worse clinical disease course measured by the MS Functional Composite Score and MS Severity Score. Low-producer allele CCR5 + 303*G was associated with reduced T2 hyperintense and T1 hypointense lesion volumes on MRI, and high-producer allele CCR5 + 303*A with early age at onset. Furthermore, low-producer allele CCR5Δ32 was associated with reduced T2 lesion volume, lower black hole ratio on MRI, and with a higher percentage of lesions with signs of remyelination, histopathologically. In summary, our multifaceted study supports the notion that polymorphisms in CCL5 and CCR5 modify the course of MS.",
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CCL5 and CCR5 genotypes modify clinical, radiological and pathological features of multiple sclerosis. / van Veen, Tineke; Nielsen, Jessica; Berkhof, Johannes; Barkhof, Frederik; Kamphorst, Wouter; Bö, Lars; Ravid, Rivka; Verweij, Cor L.; Huitinga, Inge; Polman, Chris H.; Uitdehaag, Bernard M.J.

In: Journal of Neuroimmunology, Vol. 190, No. 1-2, 01.10.2007, p. 157-164.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - CCL5 and CCR5 genotypes modify clinical, radiological and pathological features of multiple sclerosis

AU - van Veen, Tineke

AU - Nielsen, Jessica

AU - Berkhof, Johannes

AU - Barkhof, Frederik

AU - Kamphorst, Wouter

AU - Bö, Lars

AU - Ravid, Rivka

AU - Verweij, Cor L.

AU - Huitinga, Inge

AU - Polman, Chris H.

AU - Uitdehaag, Bernard M.J.

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N2 - Chemokines mediate selective recruitment of leukocyte subsets into the CNS during inflammatory episodes. We hypothesised that functional polymorphisms in CCR5 and CCL5 influence perivascular leukocyte infiltration, inflammation, axonal loss, and remyelination, and disease course. Therefore, we determined genotypes at four possibly functional polymorphisms in CCR5 and CCL5 for 637 patients and 92 brain donors with multiple sclerosis (MS). For a subset of 192 patients, MRI data were available. We found that low-producer allele CCL5-403*G was associated with reduced risk of severe axonal loss, whereas high-producer allele CCL5-403*A was associated with a worse clinical disease course measured by the MS Functional Composite Score and MS Severity Score. Low-producer allele CCR5 + 303*G was associated with reduced T2 hyperintense and T1 hypointense lesion volumes on MRI, and high-producer allele CCR5 + 303*A with early age at onset. Furthermore, low-producer allele CCR5Δ32 was associated with reduced T2 lesion volume, lower black hole ratio on MRI, and with a higher percentage of lesions with signs of remyelination, histopathologically. In summary, our multifaceted study supports the notion that polymorphisms in CCL5 and CCR5 modify the course of MS.

AB - Chemokines mediate selective recruitment of leukocyte subsets into the CNS during inflammatory episodes. We hypothesised that functional polymorphisms in CCR5 and CCL5 influence perivascular leukocyte infiltration, inflammation, axonal loss, and remyelination, and disease course. Therefore, we determined genotypes at four possibly functional polymorphisms in CCR5 and CCL5 for 637 patients and 92 brain donors with multiple sclerosis (MS). For a subset of 192 patients, MRI data were available. We found that low-producer allele CCL5-403*G was associated with reduced risk of severe axonal loss, whereas high-producer allele CCL5-403*A was associated with a worse clinical disease course measured by the MS Functional Composite Score and MS Severity Score. Low-producer allele CCR5 + 303*G was associated with reduced T2 hyperintense and T1 hypointense lesion volumes on MRI, and high-producer allele CCR5 + 303*A with early age at onset. Furthermore, low-producer allele CCR5Δ32 was associated with reduced T2 lesion volume, lower black hole ratio on MRI, and with a higher percentage of lesions with signs of remyelination, histopathologically. In summary, our multifaceted study supports the notion that polymorphisms in CCL5 and CCR5 modify the course of MS.

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