Ouma Collins, Keller Christopher C, Opondo Dorothy A, Were Tom, Otieno Richard O, Otieno Michael F, Orago Alloys S S, Ong'Echa John M, Vulule John M, Ferrell Robert E, Perkins Douglas J
University of Pittsburgh/Kenya Medical Research Institute Laboratories of Parasitic and Viral Diseases, Kisumu, Kenya.
Am J Trop Med Hyg. 2006 Apr;74(4):573-7.
Protective immunity against Plasmodium falciparum is partially mediated through binding of malaria-specific IgG antibodies to Fcgamma receptors. Polymorphic variability in Fcgamma RIIa (H/R-131) is associated with differential binding of IgG subtypes and malaria disease outcomes. However, the role of Fcgamma RIIa-131 variability in conditioning susceptibility to severe malarial anemia, the primary manifestation of severe malaria in holoendemic P. falciparum transmission areas, is largely undefined. Thus, Fcgamma RIIa-H131R polymorphism was investigated in 493 children who came to a hospital with acute malaria. Variation in Fcgamma RIIa-131 was not significantly associated with severe malarial anemia (hemoglobin [Hb] < 6.0 g/dL) or malaria anemia (Hb < 8.0 g/dL). However, relative to the heterozygous genotype, homozygotes for the R131 alleles were protected against high-density parasitemia (>or= 10,000 parasites/microL; odds ratio [OR] = 0.58, 95% confidence interval [CI] = 0.37-0.92, P = 0.02), while homozygotes for the H131 alleles were mildly protective (OR = 0.71, 95% CI = 0.45-1.13, P = 0.14). Additional multivariate analyses showed that infection with human immunodeficiency virus type 1 did not influence the associations between FcgammaRIIa-H131R polymorphism and malaria disease outcomes. Genotypic results presented here parallel data illustrating that parasite density is unrelated to the severity of anemia in children with acute malaria. Thus, although homozygosity for the R131 allele protects against high-density parasitemia, FcgammaRIIa-131 polymorphism does not protect against malaria anemia.
针对恶性疟原虫的保护性免疫部分是通过疟疾特异性IgG抗体与Fcγ受体的结合来介导的。FcγRIIa（H/R-131）的多态性变异与IgG亚型的差异结合及疟疾疾病转归相关。然而，FcγRIIa-131变异在决定严重疟疾贫血（在恶性疟原虫高度流行传播地区严重疟疾的主要表现）易感性方面的作用很大程度上尚不清楚。因此，对493名因急性疟疾前来医院就诊的儿童进行了FcγRIIa-H131R多态性研究。FcγRIIa-131的变异与严重疟疾贫血（血红蛋白[Hb]<6.0 g/dL）或疟疾贫血（Hb<8.0 g/dL）无显著关联。然而，相对于杂合基因型，R131等位基因纯合子对高密度寄生虫血症（≥10,000个寄生虫/微升；优势比[OR]=0.58，95%置信区间[CI]=0.37-0.92，P=0.02）具有保护作用，而H131等位基因纯合子具有轻度保护作用（OR=0.71，95%CI=0.45-1.13，P=0.14）。额外的多变量分析表明，感染1型人类免疫缺陷病毒并不影响FcγRIIa-H131R多态性与疟疾疾病转归之间的关联。此处呈现的基因型结果与说明寄生虫密度与急性疟疾儿童贫血严重程度无关的数据相一致。因此，尽管R131等位基因纯合性可预防高密度寄生虫血症，但FcγRIIa-131多态性并不能预防疟疾贫血。
