Abstract：
OBJECTIVE: To further substantiate the role of antibody-mediated complement activation in multifocal motor neuropathy (MMN) immunopathology, we investigated the distribution of promotor polymorphisms of genes encoding the membrane-bound complement regulators CD46, CD55, and CD59 in patients with MMN and controls, and evaluated their association with disease course.
METHODS: We used Sanger sequencing to genotype five common polymorphisms in the promotor regions of CD46, CD55, and CD59 in 133 patients with MMN and 380 controls. We correlated each polymorphism to clinical parameters.
RESULTS: The genotype frequencies of rs28371582, a 21-bp deletion in the CD55 promotor region, were altered in patients with MMN as compared to controls (p .009; Del/Del genotype 16.8% vs. 7.7%, p .005, odds ratio: 2.43 [1.27-4.58]), and patients carrying this deletion had a more favorable disease course (mean difference 0.26 Medical Research Council [MRC] points/year; 95% confidence interval [CI]: 0.040-0.490, p .019). The presence of CD59 rs141385724 was associated with less severe pre-diagnostic disease course (mean difference 0.940 MRC point/year; 95% CI: 0.083-1.80, p .032).
CONCLUSIONS: MMN susceptibility is associated with a 21-bp deletion in the CD55 promotor region (rs2871582), which is associated with lower CD55 expression. Patients carrying this deletion may have a more favorable long-term disease outcome. Taken together, these results point out the relevance of the pre-C5 level of the complement cascade in the inflammatory processes underlying MMN.
METHODS: We used Sanger sequencing to genotype five common polymorphisms in the promotor regions of CD46, CD55, and CD59 in 133 patients with MMN and 380 controls. We correlated each polymorphism to clinical parameters.
RESULTS: The genotype frequencies of rs28371582, a 21-bp deletion in the CD55 promotor region, were altered in patients with MMN as compared to controls (p .009; Del/Del genotype 16.8% vs. 7.7%, p .005, odds ratio: 2.43 [1.27-4.58]), and patients carrying this deletion had a more favorable disease course (mean difference 0.26 Medical Research Council [MRC] points/year; 95% confidence interval [CI]: 0.040-0.490, p .019). The presence of CD59 rs141385724 was associated with less severe pre-diagnostic disease course (mean difference 0.940 MRC point/year; 95% CI: 0.083-1.80, p .032).
CONCLUSIONS: MMN susceptibility is associated with a 21-bp deletion in the CD55 promotor region (rs2871582), which is associated with lower CD55 expression. Patients carrying this deletion may have a more favorable long-term disease outcome. Taken together, these results point out the relevance of the pre-C5 level of the complement cascade in the inflammatory processes underlying MMN.
摘要：
目的：进一步证实抗体介导的补体激活在多灶性运动神经病（MMN）免疫病理中的作用，我们调查了MMN患者和对照组中编码膜结合补体调节因子CD46，CD55和CD59的基因启动子多态性的分布，并评估了它们与病程的关系。
方法：我们使用Sanger测序对133例MMN患者和380例对照的CD46、CD55和CD59启动子区域的5个常见多态性进行了基因分型。我们将每个多态性与临床参数相关联。
结果：rs28371582的基因型频率，CD55启动子区的21bp缺失，与对照组相比，MMN患者的改变(p.009；Del/Del基因型16.8%与7.7%,p.005，赔率比：2.43[1.27-4.58])，并且携带该缺失的患者的病程更有利（平均差0.26医学研究委员会[MRC]点/年；95％置信区间[CI]：0.040-0.490，第019页）。CD59rs141385724的存在与较不严重的预诊断病程相关（平均差异0.940MRC点/年；95％CI：0.083-1.80，p.032）。
结论：MMN易感性与CD55启动子区的21bp缺失相关（rs2871582），这与较低的CD55表达有关。携带这种缺失的患者可能具有更有利的长期疾病结果。一起来看,这些结果指出补体级联前C5水平在MMN基础的炎症过程中的相关性.
方法：我们使用Sanger测序对133例MMN患者和380例对照的CD46、CD55和CD59启动子区域的5个常见多态性进行了基因分型。我们将每个多态性与临床参数相关联。
结果：rs28371582的基因型频率，CD55启动子区的21bp缺失，与对照组相比，MMN患者的改变(p.009；Del/Del基因型16.8%与7.7%,p.005，赔率比：2.43[1.27-4.58])，并且携带该缺失的患者的病程更有利（平均差0.26医学研究委员会[MRC]点/年；95％置信区间[CI]：0.040-0.490，第019页）。CD59rs141385724的存在与较不严重的预诊断病程相关（平均差异0.940MRC点/年；95％CI：0.083-1.80，p.032）。
结论：MMN易感性与CD55启动子区的21bp缺失相关（rs2871582），这与较低的CD55表达有关。携带这种缺失的患者可能具有更有利的长期疾病结果。一起来看,这些结果指出补体级联前C5水平在MMN基础的炎症过程中的相关性.
