Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM Universite Libre de Bruxelles, Gosselies Campus, Gosselies, Hainaut, Belgium.
Molecular and Cell Biology Laboratory, Biotechnology Unit, Faculty of Science, University of Buea, Buea, Cameroon.
PLoS One. 2018 Sep 26;13(9):e0202915. doi: 10.1371/journal.pone.0202915. eCollection 2018.
Onchocerciasis is a severely debilitating yet neglected tropical disease (NTD) that creates social stigma, generates and perpetuates poverty, and leads ultimately in some cases to irreversible unilateral or bilateral blindness if untreated. Consequently, the disease is a major impediment to socioeconomic development. Many control programs have been launched for the disease with moderate successes achieved. This mitigated hit is partially due to the lingering need for reliable, non-invasive and easily applicable tools for mapping endemic regions and post-elimination surveillance. In this work, bioinformatics analyses combined with immunological assays were applied in a bid to develop potential tools for diagnosis and assessing the success of drug treatment programs. We report that (i) the O. volvulus antigen, Ov58GPCR is a G-protein coupled receptor (GPCR) conserved in related nematodes, (ii) synthetic peptides predicted to be in the extracellular domain (ECD) of Ov58GPCR are indeed immunogenic epitopes in actively-infected individuals, (iii) synthetic peptide cocktails discriminate between actively-infected individuals, treated individuals and healthy African controls, (iv) polyclonal antibodies against one of the peptides or against the bacterially-expressed ECD reacted specifically with the native antigen of O. volvulus total and surface extracts, (v) Ov58GPCR is transcribed in both larvae and adult parasite stages, (vi) IgG and IgE responses to the recombinant ECD decline with ivermectin treatment. All these findings suggest that the extracellular domain and synthetic peptides of Ov58GPCR, as well as the specific immune response generated could be harnessed in the context of disease diagnosis and surveillance.
盘尾丝虫病是一种严重的使人丧失能力但被忽视的热带病（NTD），它会造成社会耻辱，引发和加剧贫困，并最终在某些情况下导致不可逆转的单侧或双侧失明，如果不治疗的话。因此，这种疾病是社会经济发展的主要障碍。已经为这种疾病发起了许多控制项目，并取得了一定的成功。这种部分缓解的情况部分归因于仍然需要可靠、非侵入性和易于应用的工具来绘制流行地区地图和进行消除后监测。在这项工作中，生物信息学分析与免疫学检测相结合，旨在开发潜在的诊断工具和评估药物治疗方案的成功。我们报告称：（i）盘尾丝虫抗原 Ov58GPCR 是一种在相关线虫中保守的 G 蛋白偶联受体（GPCR），（ii）预测位于 Ov58GPCR 细胞外结构域（ECD）的合成肽实际上是在活动性感染个体中具有免疫原性的表位，（iii）合成肽混合物能够区分活动性感染个体、治疗个体和健康的非洲对照个体，（iv）针对其中一种肽或针对细菌表达的 ECD 的多克隆抗体与 O. volvulus 总蛋白和表面提取物的天然抗原特异性反应，（v）Ov58GPCR 在幼虫和成虫寄生虫阶段都有转录，（vi）针对重组 ECD 的 IgG 和 IgE 反应随着伊维菌素治疗而下降。所有这些发现表明，Ov58GPCR 的细胞外结构域和合成肽以及产生的特异性免疫反应可以在疾病诊断和监测的背景下得到利用。
