Cabantous Sandrine, Poudiougou Belco, Traore Abdoulaye, Keita Marouf, Cisse Mamadou Balla, Doumbo Ogobara, Dessein Alain J, Marquet Sandrine
Immunology and Genetics of Parasitic Diseases, INSERM UMR399, Faculty of Medicine Timone, Universite de la Mediterranee, Marseille, France.
J Infect Dis. 2005 Sep 1;192(5):854-60. doi: 10.1086/432484. Epub 2005 Jul 22.
The pathogenic mechanisms of cerebral malaria (CM) are unclear but are thought to involve cytokine-mediated inflammation enhanced by parasite sequestration in the brain microcirculation. The role that interferon (IFN)-gamma could play that would enhance inflammation but also reduce parasitemia is unclear.
Plasma IFN-gamma concentrations were measured by enzyme-linked immunosorbent assay in 96 children with CM and 40 children with uncomplicated malaria (UM) who had been recruited from Gabriel Toure Hospital (Bamako, Mali). We investigated the relationship between IFN- gamma concentrations and disease by nonparametric analysis. Polymorphisms in IFNG were characterized by restriction enzyme analysis or size-determination electrophoresis. Associations between polymorphisms and CM were evaluated by the family-based association test on 240 families.
During episodes of malaria, IFN-gamma concentrations were lower in children with CM than in children with UM (P = .007). IFNG-183T (P = .009) and IFNG-183G/T (P = .013) were found to be less frequent than expected in children with CM. A trend toward association was also observed between IFNG(CA)14/(CA)14 (P = .073) and CM. The IFNG-183G/T and IFNG(CA)14/(CA)14 genotypes were more frequent in children with UM than in children with CM (odds ratio, 0.30 and 0.34, respectively).
The low plasma IFN- gamma concentrations in children with CM and the associations between a reduced risk of CM and (1) the IFNG-183T allele (which increases gene transcription) and (2) the IFNG-183G/T genotype are consistent with the concept that IFN-gamma protects against CM.
脑型疟疾（CM）的致病机制尚不清楚，但一般认为其涉及细胞因子介导的炎症反应，这种炎症反应会因寄生虫在脑微循环中的滞留而增强。干扰素（IFN）-γ在增强炎症反应的同时还能降低寄生虫血症，其具体作用尚不清楚。
采用酶联免疫吸附测定法，对从加布里埃尔·图雷医院（马里巴马科）招募的96例脑型疟疾患儿和40例非重症疟疾（UM）患儿的血浆IFN-γ浓度进行了检测。我们通过非参数分析研究了IFN-γ浓度与疾病之间的关系。通过限制性酶切分析或大小测定电泳对IFNG基因多态性进行了表征。采用基于家系的关联检验，在240个家庭中评估了基因多态性与脑型疟疾之间的关联。
在疟疾发作期间，脑型疟疾患儿的IFN-γ浓度低于非重症疟疾患儿（P = 0.007）。发现IFNG-183T（P = 0.009）和IFNG-183G/T（P = 0.013）在脑型疟疾患儿中的出现频率低于预期。在IFNG(CA)14/(CA)14与脑型疟疾之间也观察到了一种关联趋势（P = 0.073）。IFNG-183G/T和IFNG(CA)14/(CA)14基因型在非重症疟疾患儿中的出现频率高于脑型疟疾患儿（优势比分别为0.30和0.34）。
脑型疟疾患儿血浆IFN-γ浓度较低，以及CM风险降低与（1）IFNG-183T等位基因（可增加基因转录）和（2）IFNG-183G/T基因型之间的关联，均与IFN-γ可预防CM的概念相符。
