Fitzsimmons Colin M, McBeath Rowena, Joseph Sarah, Jones Frances M, Walter Klaudia, Hoffmann Karl F, Kariuki H Curtis, Mwatha Joseph K, Kimani Guchuhi, Kabatereine Narcis B, Vennervald Birgitte J, Ouma John H, Dunne David W
Department of Pathology, University of Cambridge, Cambridge, UK.
Int Arch Allergy Immunol. 2007;142(1):40-50. doi: 10.1159/000095997. Epub 2006 Oct 2.
The human IgE response is associated with allergy and with host defence against parasitic worms. A response to Sm22.6, the dominant IgE antigen in adult Schistosoma mansoni worms, correlates with resistance to re-infection after treatment. Sm22.6 is one of a family of EF-hand containing parasite proteins with sequence similarity to dynein light chain (DLC) and with major non-parasite allergens. Here we compare human IgE and IgG responses to other family members, Sm20.8 and Sm21.7, as well as to SmDLC1, relating these to antigen structure and expression in parasite life stages.
Recombinant antigens were used in ELISA to measure antibody isotype responses in 177 cases from an endemic area, before and 7 weeks after treatment. Parasite antigen expression was assessed by RT-PCR and Western blotting.
Levels of antibodies to Sm22.6 and Sm20.8 (but not to Sm21.7 or SmDLC1) showed posttreatment increases in all but young children. Many produced IgE to Sm22.6 and Sm20.8 (2 EF-hands), few to Sm21.7 (1 EF-hand) or SmDLC1 (no EF-hands). Sm21.7 was expressed in cercariae, adults and eggs, Sm22.6 and Sm20.8 were concentrated in the adult.
These studies suggest that IgE antigens Sm22.6 and Sm20.8 are only released to boost antibodies when adult worms die, whilst Sm21.7 and SmDLC1 are released constantly from eggs dying in host tissue. IgE responses to these allergen-like molecules may be influenced by patterns of exposure and the number of EF-hand motifs.
人类IgE反应与过敏以及宿主抵御寄生虫感染有关。对曼氏血吸虫成虫中主要的IgE抗原Sm22.6的反应与治疗后抵抗再次感染相关。Sm22.6是一类含有EF手结构的寄生虫蛋白家族成员之一,其序列与动力蛋白轻链(DLC)相似,且与主要的非寄生虫过敏原相似。在此,我们比较人类对其他家族成员Sm20.8和Sm21.7以及SmDLC1的IgE和IgG反应,并将这些反应与抗原结构以及在寄生虫生活阶段的表达相关联。
使用重组抗原来通过ELISA检测来自流行区的177例患者在治疗前和治疗7周后的抗体同种型反应。通过RT-PCR和蛋白质印迹法评估寄生虫抗原的表达。
除幼儿外,所有患者体内针对Sm22.6和Sm20.8(但不包括Sm21.7或SmDLC1)的抗体水平在治疗后均有所升高。许多人产生了针对Sm22.6和Sm20.8(含2个EF手结构)的IgE,很少有人产生针对Sm21.7(含1个EF手结构)或SmDLC1(不含EF手结构)的IgE。Sm21.7在尾蚴、成虫和虫卵中均有表达,Sm22.6和Sm20.8集中在成虫中。
这些研究表明,IgE抗原Sm22.6和Sm20.8仅在成虫死亡时释放以增强抗体,而Sm21.7和SmDLC1则从宿主组织中死亡的虫卵中持续释放。对这些类过敏原分子的IgE反应可能受暴露模式和EF手基序数量的影响。