Association between combined properdin and mannose-binding lectin deficiency and infection with Neisseria meningitidi
Association between combined properdin and mannose-binding lectin deficiency and infection with Neisseria meningitidi
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DOI：
10.1016/j.molimm.2005.02.017
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发表时间：
2006-02-01
影响因子：
3.6
通讯作者：
Wang, P
中科院分区：
文献类型：
--
作者：
Bathum, L;Hansen, H;Wang, P
背景：备解素基因缺陷的个体更易患脑膜炎球菌病。同样，甘露糖结合凝集素（MBL）的低浓度或生物活性降低与儿童期细菌感染的发生率较高有关。在这项研究中，我们报告了我们的研究结果在丹麦的家庭脑膜炎球菌脑膜炎的发病率非常高，共4例，其中之一fatal.Methods：：备解素和MBL定量ELISA和备解素基因进行了筛选，使用变性高效液相色谱法（DHPLC）和随后的测序异常模式的序列变异。对MBL基因的三种已知变异等位基因（B、C和D）以及三种启动子多态性（-221 Y/X、-550 H/L和+4 P/Q）进行基因分型。结果：：六分之二检测不到备解素活性的男性患有脑膜炎。他们也有低MBL血清水平或携带MBL变异等位基因，而高MBL浓度测量在四分之三的备解素缺乏男性-没有脑膜炎。外显子10中的剪接位点突变（c. 1487-2A > G）在备解素基因中被发现，并与生化测定的备解素缺陷共分离。结论：我们的研究结果表明，备解素和MBL的联合缺陷增加了脑膜炎奈瑟菌感染的风险，并强调了上位性遗传相互作用在疾病易感性中的重要性。(c)2005爱思唯尔有限公司保留所有权利。
Background:: Individuals genetically deficient of properdin are more susceptible to meningococcal disease. Likewise low concentration or decreased biological activity of mannose-binding lectin (MBL) is associated with higher incidence of bacterial infections during childhood. In this study we report our findings in a Danish family with a remarkably high incidence of meningococcal meningitis-in total four cases, one of them fatal.Methods:: Properdin and MBL were quantified by ELISA and the properdin gene was screened for sequence variations using denaturing high-performance liquid chromatography (DHPLC) and subsequent sequencing of abnormal patterns. The MBL gene was genotyped for the three known variant alleles (B, C and D) as well as three promoter polymorphisins (-221 Y/X, -550 H/L and +4P/Q).Results:: Two out of six males with undetectable properdin activity had meningitis. They had also low MBL serum levels or carried an MBL variant allele, whereas high MBL concentrations were measured in three out of four properdin deficient males-without meningitis. A splice site mutation in exon 10 (c. 1487-2A > G) was found in the properdin gene and co segregated with biochemically measured properdin deficiency.Conclusion:: Our results indicate that a combined deficiency of both properdin and MBL increases the risk of infection with Neisseria meningitidis and stress the importance of epistatic genetic interactions in disease susceptibility. (c) 2005 Elsevier Ltd. All rights reserved.