The CCR5 deletion mutation fails to protect against multiple sclerosis
The CCR5 deletion mutation fails to protect against multiple sclerosis
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DOI：
10.1016/s0198-8859(97)00207-3
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发表时间：
1997-11-01
期刊：
影响因子：
2.7
通讯作者：
Stewart, GJ
中科院分区：
文献类型：
--
作者：
Bennetts, BH;Teutsch, SM;Stewart, GJ
在对趋化因子及其受体的理解和鉴定方面的最新进展为将其作为MS遗传易感性/抗性的候选位点提供了证据，在MS患者和EAE小鼠的脑脊液中均发现了趋化因子巨噬细胞炎症蛋白(MIP)-1 α的水平升高，并且抗MIP-1 α抗体已被证明可以预防EAE。最近，MIP-1 α的主要受体趋化因子受体5 （CCR5）基因中出现了一种常见的缺失突变。突变的纯合子不能表达这种受体。此外，纯合子对HIV感染具有高度的保护作用，这对感染因子在其他可能涉及病毒成分的多因子疾病中进入细胞具有潜在的影响。鉴于这些方面，我们筛选了120名无血缘关系的澳大利亚复发/缓解型MS患者和168名无血缘关系的对照受试者，以检测CCR5 Delta 32突变。MS患者CCR5 Delta 32基因等位基因频率（0.1125）与对照组（0.0921）差异无统计学意义。MS患者中两个CCR5 Delta 32纯合子的存在表明，CCR5的缺失对MS没有保护作用。这些数据表明，CCR5不是MS表达的必要成分，尽管这可能是由于趋化因子系统中的冗余，当CCR5缺失时，不同的趋化因子受体可以替代CCR5。(C)美国组织相容性和免疫遗传学学会，1997。Elsevier Science Inc.出版。
Recent advances in the understanding and identification of chemokines and their receptors have provided evidence for their consideration as candidate loci with respect to genetic susceptibility/resistance to MS. Increased levels of the chemokine, macrophage inflammatory protein (MIP)-1 alpha, have been demonstrated in the cerebrospinal fluid of both patients with MS and mice with EAE, and anti-MIP-1 alpha antibodies have been shown to prevent EAE.Recently, a common deletion mutation in the gene for the major receptor for MIP-1 alpha, chemokine receptor 5 (CCR5) has been described. Homozygotes for the mutation fail to express this receptor. Moreover, homozygotes are highly protected against HIV infection, this has potential implications for the cell entry of infectious agents in other multifactorial diseases where a viral component may be involved. In view of these aspects, a group of 120 unrelated Australian relapsing/remitting MS and 168 unrelated control subjects were screened for the CCR5 Delta 32 mutation. There was no significant difference in the allele frequency of CCR5 Delta 32 gene between the MS patients (0.1125) and the control population (0.0921). The presence of two CCR5 Delta 32 homozygotes in the MS patients indicates that the absence of CCR5 is not protective against MS. These data suggest that CCR5 is not an essential component in MS expression, though this may be due to redundancy in the chemokine system where different chemokine receptors may substitute for CCR5 when it is absent. (C) American Society for Histocompatibility and Immunogenetics, 1997. Published by Elsevier Science Inc.