Parasitology Department, Medical Faculty, Shahid Beheshti University of Medical Science, Tehran, Iran.
Med Hypotheses. 2013 Oct;81(4):557-60. doi: 10.1016/j.mehy.2013.07.003. Epub 2013 Jul 24.
Cystic echinococcosis (CE) is caused by the larval stage of the tapeworm Echinococcus granulosus. Until now, CE does not have an effective follow-up after surgery. To date, CE follow-up is conducted based on either antibody or antigen detection assays by double antibody sandwich ELISA. Unlike antigen detection, antibodies to imply exposure to an Echinococcus infection while their titration could remain for a longer period (1-10years) after surgery. Likewise, antibody respond may be related to the location of a mature hydatid cyst. Antigen detection shows presence of CE infection, it is extremely important and necessary in follow-up of CE after surgery. The circulating antigen (CAg) titration decrease faster than circulating antibody (during 1-3weeks) after operation. Location of hydatid cyst in detecting antigen is affected less than antibody also. Regarding this subject, antigen detection has several limitations that lead to be used less in CE follow-up. Although, AgB 8/1-kDa subunit is considered as a principle and immunogenic CAg but sensitivity of CAg detection compared to with antibody has variable range, between 33% and 85% which owing to formation of circulating immune complexes (CICs) in result of antigen - antibody complex. The another problem is non using specific CAg (AgB 8/1-kDa subunit) for production of specific paratopes (rabbit hyper immune antiserum) against AgB 8/1-kDa which is used as capture (primary) antibody in double antibody sandwich ELISA assay. The designation of synthetic peptides from conserved regions of AgB 8/1-kDa can help to this problem. These regions (motifs) should be selected for allelic, dominant, immunogenic and conserved without any genetic variation. The first part of this hypothesis suggests which patient's sera should be treated with acidic buffers such as boric acid, acetic acid, glycine/HCl, polyethylene glycol (PEG) or combination of each of them accompanied by boiling patient's sera which causes breaking Ag-Ab complexes and in result of releasing AgB 8/1. These modifications are effective to releasing CAg from CIC. To date, the synthetic peptides have been widely used in CE serodiagnosis based on circulating antibody detection only. In second part of this hypothesis suggests the using synthetic peptide of p176 derived AgB 8/1-kDa subunit containing conserved specific epitopes for preparation of specific paratopes (rabbit hyper immune antiserum) based on CAg detection. So, there is no need any native antigens for preparation of non-specific rabbit hyper immune antiserum. These novel improvements can help to decrease the cross-reactivity with other parasitic diseases (specificity). Increasing antigen detection could make a chance in sensitivity of patient's sera and in result of the best and suitable tool for CE follow-up.
囊性包虫病 (CE) 是由绦虫细粒棘球蚴的幼虫阶段引起的。到目前为止,CE 在手术后没有有效的随访。迄今为止,CE 的随访是基于双抗体夹心 ELISA 进行的抗体或抗原检测。与抗原检测不同,抗体暗示暴露于包虫感染,而其效价在手术后可延长一段时间(1-10 年)。同样,抗体反应可能与成熟包虫囊肿的位置有关。抗原检测显示存在 CE 感染,这在手术后的 CE 随访中非常重要和必要。手术切除后,循环抗原 (CAg) 的滴度下降速度比循环抗体(1-3 周)更快。在检测抗原时,包虫囊肿的位置对抗体的影响也较小。关于这个问题,抗原检测有几个限制,导致在 CE 随访中使用较少。尽管 AgB 8/1-kDa 亚基被认为是一种主要的免疫原性 CAg,但 CAg 检测的敏感性与抗体的敏感性相比,范围在 33%到 85%之间,这是由于抗原-抗体复合物形成循环免疫复合物 (CICs) 所致。另一个问题是不使用特异性 CAg(AgB 8/1-kDa 亚基)来产生针对 AgB 8/1-kDa 的特异性配对抗体(兔高免疫抗血清),AgB 8/1-kDa 用作双抗体夹心 ELISA 测定中的捕获(初级)抗体。从 AgB 8/1-kDa 的保守区域设计合成肽可以帮助解决这个问题。这些区域(基序)应选择等位基因、显性、免疫原性和保守,没有任何遗传变异。该假设的第一部分表明,应该用硼酸、乙酸、甘氨酸/HCl、聚乙二醇 (PEG) 或它们的组合处理患者的血清,同时煮沸患者的血清,这会导致打破 Ag-Ab 复合物,并导致 AgB 8/1 的释放。这些修饰对于从 CIC 中释放 CAg 是有效的。到目前为止,合成肽已广泛用于基于循环抗体检测的 CE 血清诊断。在该假设的第二部分中,建议使用源自 AgB 8/1-kDa 亚基的 p176 衍生的合成肽,该肽含有针对 CAg 检测的保守特异性表位,用于制备特异性配对抗体(兔高免疫抗血清)。因此,制备非特异性兔高免疫抗血清不需要任何天然抗原。这些新的改进可以帮助减少与其他寄生虫病的交叉反应(特异性)。增加抗原检测可以提高患者血清的敏感性,成为 CE 随访的最佳和合适工具。