Proof of concept: A bioinformatic and serological screening method for identifying new peptide antigens for Chlamydia trachomatis related sequelae in women
Scott H. Stansfield , Pooja Patel , Joseph Debattista , Charles W. Armitage , Kelly Cunningham , Peter Timms , John Allan , Aruna Mittal , Wilhelmina M. Huston
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引用次数: 15
Abstract
This study aimed to identify new peptide antigens from Chlamydia (C.) trachomatis in a proof of concept approach which could be used to develop an epitope-based serological diagnostic for C. trachomatis related infertility in women. A bioinformatics analysis was conducted examining several immunodominant proteins from C. trachomatis to identify predicted immunoglobulin epitopes unique to C. trachomatis. A peptide array of these epitopes was screened against participant sera. The participants (all female) were categorized into the following cohorts based on their infection and gynecological history; acute (single treated infection with C. trachomatis), multiple (more than one C. trachomatis infection, all treated), sequelae (PID or tubal infertility with a history of C. trachomatis infection), and infertile (no history of C. trachomatis infection and no detected tubal damage). The bioinformatics strategy identified several promising epitopes. Participants who reacted positively in the peptide 11 ELISA were found to have an increased likelihood of being in the sequelae cohort compared to the infertile cohort with an odds ratio of 16.3 (95% c.i. 1.65–160), with 95% specificity and 46% sensitivity (0.19–0.74). The peptide 11 ELISA has the potential to be further developed as a screening tool for use during the early IVF work up and provides proof of concept that there may be further peptide antigens which could be identified using bioinformatics and screening approaches.
本研究旨在通过概念验证方法从沙眼衣原体(C.)中鉴定新的肽抗原,可用于开发基于表位的女性沙眼衣原体相关不孕的血清学诊断。对沙眼原体的几种免疫优势蛋白进行了生物信息学分析,以确定沙眼原体特有的预测免疫球蛋白表位。针对参与者血清筛选这些表位的肽阵列。参与者(均为女性)根据其感染和妇科病史分为以下队列:急性(单次沙眼衣原体感染治疗)、多发性(一次以上沙眼衣原体感染,全部治疗)、后遗症(有沙眼衣原体感染史的盆腔炎或输卵管不孕)和不孕症(无沙眼衣原体感染史,未发现输卵管损伤)。生物信息学策略确定了几个有希望的表位。与不育队列相比,肽11酶联免疫吸附试验阳性的参与者出现后遗症队列的可能性增加,比值比为16.3 (95% ci . 1.65-160),特异性为95%,敏感性为46%(0.19-0.74)。肽11酶联免疫吸附试验具有进一步发展的潜力,可作为早期试管婴儿工作的筛选工具,并提供概念证明,可能存在进一步的肽抗原,可以使用生物信息学和筛选方法进行鉴定。