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

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• 作者：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
• 关键词：Multiple sclerosis ; Genetic ; Severity ; Pathology ; MRI
• 刊名：Journal of Neuroimmunology
• 出版年：2007
• 期刊代码：32_01655728
• 类别：neu
• 出版时间：October 2007
• 卷：190
• 期：1-2
• 页码：157-164
• 文件大小：359 K

摘要

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 CCL5–403G was associated with reduced risk of severe axonal loss, whereas high-producer allele CCL5–403A was associated with a worse clinical disease course measured by the MS Functional Composite Score and MS Severity Score. Low-producer allele CCR5 + 303G was associated with reduced T2 hyperintense and T1 hypointense lesion volumes on MRI, and high-producer allele CCR5 + 303A 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.