Garred Peter, Nielsen Morten A, Kurtzhals Jørgen A L, Malhotra Rajneesh, Madsen Hans O, Goka Bamenla Q, Akanmori Bartholomew D, Sim Robert B, Hviid Lars
Tissue Typing Laboratory-7631, Department of Clinical Immunology, Rigshospitalet, Copenhagen, Denmark.
Infect Immun. 2003 Sep;71(9):5245-53. doi: 10.1128/IAI.71.9.5245-5253.2003.
Variant alleles in the mannose-binding lectin (MBL) gene (mbl2) causing low levels of functional MBL are associated with susceptibility to different infections and are common in areas where malaria is endemic. Therefore, we investigated whether MBL variant alleles in 551 children from Ghana were associated with the occurrence and outcome parameters of Plasmodium falciparum malaria and asked whether MBL may function as an opsonin for P. falciparum. No difference in MBL genotype frequency was observed between infected and noninfected children or between children with cerebral malaria and/or severe malarial anemia and children with uncomplicated malaria. However, patients with complicated malaria who were homozygous for MBL variant alleles had significantly higher parasite counts and lower blood glucose levels than their MBL-competent counterparts. Distinct calcium-dependent binding of MBL to the membrane of P. falciparum-infected erythrocytes, which could be inhibited by mannose, was observed. Further characterization revealed that MBL reacted with a P. falciparum glycoprotein identical to the 78-kDa glucose-regulated stress protein of P. falciparum. MBL seems to be a disease modifier in clinical malaria and to function as an opsonin for erythrocytes invaded by P. falciparum and may thus be involved in sequestration of the parasite, which in turn may explain the association between homozygosity for MBL variant alleles and high parasite counts.
甘露糖结合凝集素（MBL）基因（mbl2）中的变异等位基因导致功能性MBL水平低下，与易患不同感染相关，且在疟疾流行地区很常见。因此，我们调查了来自加纳的551名儿童中MBL变异等位基因是否与恶性疟原虫疟疾的发生及转归参数相关，并询问MBL是否可能作为恶性疟原虫的调理素发挥作用。在感染儿童与未感染儿童之间，或在患有脑型疟疾和/或严重疟性贫血的儿童与患有非复杂性疟疾的儿童之间，未观察到MBL基因型频率存在差异。然而，MBL变异等位基因纯合的复杂性疟疾患者比具有MBL功能的患者寄生虫计数显著更高，血糖水平更低。观察到MBL与恶性疟原虫感染红细胞膜存在明显的钙依赖性结合，这种结合可被甘露糖抑制。进一步的特性分析表明，MBL与一种与恶性疟原虫78 kDa葡萄糖调节应激蛋白相同的恶性疟原虫糖蛋白发生反应。MBL似乎是临床疟疾中的一种疾病修饰因子，可作为恶性疟原虫入侵红细胞的调理素发挥作用，因此可能参与寄生虫的滞留，这反过来可能解释了MBL变异等位基因纯合与高寄生虫计数之间的关联。
