白细胞介素 4 基因多态性和既往疟疾感染经历可调节复杂和无并发症疟疾患者抗疟原虫抗体的同种型谱。
IL4 gene polymorphism and previous malaria experiences manipulate anti-Plasmodium falciparum antibody isotype profiles in complicated and uncomplicated malaria.
机构信息
Department of Microbiology and Immunology, Faculty of Tropical Medicine, Mahidol University, 420/6 Rajvithi Road, Bangkok 10400, Thailand.
出版信息
Malar J. 2009 Dec 10;8:286. doi: 10.1186/1475-2875-8-286.
BACKGROUND
The IL4-590 gene polymorphism has been shown to be associated with elevated levels of anti-Plasmodium falciparum IgG antibodies and parasite intensity in the malaria protected Fulani of West Africa. This study aimed to investigate the possible impact of IL4-590C/T polymorphism on anti-P. falciparum IgG subclasses and IgE antibodies levels and the alteration of malaria severity in complicated and uncomplicated malaria patients with or without previous malaria experiences.
METHODS
Anti-P.falciparum IgG subclasses and IgE antibodies in plasma of complicated and uncomplicated malaria patients with or without previous malaria experiences were analysed using ELISA. IL4-590 polymorphisms were genotyped using RFLP-PCR. Statistical analyses of the IgG subclass levels were done by Oneway ANOVA. Genotype differences were tested by Chi-squared test.
RESULTS
The IL4-590T allele was significantly associated with anti-P. falciparum IgG3 antibody levels in patients with complicated (P = 0.031), but not with uncomplicated malaria (P = 0.622). Complicated malaria patients with previous malaria experiences carrying IL4-590TT genotype had significantly lower levels of anti-P. falciparum IgG3 (P = 0.0156), while uncomplicated malaria patients with previous malaria experiences carrying the same genotype had significantly higher levels (P = 0.0206) compared to their IL4-590 counterparts. The different anti-P. falciparum IgG1 and IgG3 levels among IL4 genotypes were observed. Complicated malaria patients with previous malaria experiences tended to have lower IgG3 levels in individuals carrying TT when compared to CT genotypes (P = 0.075). In contrast, complicated malaria patients without previous malaria experiences carrying CC genotype had significantly higher anti-P. falciparum IgG1 than those carrying either CT or TT genotypes (P = 0.004, P = 0.002, respectively).
CONCLUSION
The results suggest that IL4-590C or T alleles participated differently in the regulation of anti-malarial antibody isotype profiles in primary and secondary malaria infection and, therefore, could play an important role in alteration of malaria severity.
背景
IL4-590 基因多态性与西非人富拉尼族中升高的抗疟原虫 IgG 抗体和寄生虫载量有关。本研究旨在探讨 IL4-590C/T 多态性对有或无既往疟疾史的复杂和非复杂疟疾患者的抗疟原虫 IgG 亚类和 IgE 抗体水平以及疟疾严重程度改变的可能影响。
方法
采用 ELISA 法检测有或无既往疟疾史的复杂和非复杂疟疾患者血浆中的抗疟原虫 IgG 亚类和 IgE 抗体。采用 RFLP-PCR 法检测 IL4-590 多态性。采用单因素方差分析（Oneway ANOVA）对 IgG 亚类水平进行统计分析。采用卡方检验检测基因型差异。
结果
IL4-590T 等位基因与复杂型疟疾患者（P = 0.031）但与非复杂型疟疾患者（P = 0.622）的抗疟原虫 IgG3 抗体水平显著相关。有既往疟疾史的携带 IL4-590TT 基因型的复杂型疟疾患者的抗疟原虫 IgG3 水平显著较低（P = 0.0156），而有既往疟疾史的携带相同基因型的非复杂型疟疾患者的抗疟原虫 IgG3 水平显著较高（P = 0.0206），与 IL4-590 相比。观察到不同的 IL4 基因型之间的抗疟原虫 IgG1 和 IgG3 水平不同。与 CT 基因型相比，有既往疟疾史的复杂型疟疾患者携带 TT 时的 IgG3 水平较低（P = 0.075）。相反，无既往疟疾史的复杂型疟疾患者携带 CC 基因型的抗疟原虫 IgG1 水平明显高于携带 CT 或 TT 基因型的患者（P = 0.004，P = 0.002）。
结论
结果表明，IL4-590C 或 T 等位基因在原发性和继发性疟疾感染中以不同的方式参与调节抗疟抗体同种型谱，因此可能在疟疾严重程度改变中发挥重要作用。
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