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用于梅毒诊断和治疗预后的脂蛋白抗原表位设计

Design of Epitopes from Lipoprotein Antigens for Syphilis Diagnosis and Treatment Prognosis.

作者信息

Borghezan Letícia Alves, de Sousa Machado Lara Cândida, Neves Oliveira Iara Barreto, Fagundes Mírian Ívens, Apolidório Nicoly Silveira, Dutra da Silva Renato Canevari, Freire Victor Garcia, Schafer Antonio Augusto, Scussel Rahisa, Machado-de-Ávila Ricardo Andrez

机构信息

Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Universitário, 88806-000 Criciúma, Santa Catarina, Brazil.

Faculdade de Medicina, Universidade de Rio Verde, Fazenda Fontes do Saber, Campus Universitário, 75901-970 Rio Verde, Goiás, Brazil.

出版信息

ACS Infect Dis. 2025 Jun 13;11(6):1606-1622. doi: 10.1021/acsinfecdis.5c00155. Epub 2025 May 23.

Abstract

Syphilis, a multistage sexually transmitted infection, causes severe complications if untreated. Accurate diagnosis remains difficult due to the low protein content of and in vitro culture difficulty. Advances in immunoproteomics have identified key antigens that enhance diagnostic accuracy. Epitopes of immunodominant antigen proteins Tp0171, Tp0435, Tp0574, Tp0684, and Tp0453 were designed by bioinformatics tools, and mimetic peptides were chemically synthesized. A diagnostic accuracy cross-sectional study was performed to validate a prototype technology as a serodiagnosis platform for syphilis. Five peptides were used as antigens in a peptide-based ELISA against serum samples from syphilis-positive or noninfected patients ( = 122). CE0435 achieved 100% sensitivity and specificity with a high accuracy. The peptides CE0171 and CE0574 demonstrated high diagnostic performance, with sensitivity above 83% and specificity >90%. Peptides CE0684 and CE0453 exhibited sensitivity above 80% and 90%, respectively; CE0453 showed reduced specificity (∼66%). The peptides CE0435 and CE0171 maintained high diagnostic accuracy across syphilis stages, with a sensitivity above 83% and a specificity exceeding 97%. Peptides CE0435 and CE0171 effectively monitored syphilis treatment, as evidenced by the significant post-treatment decline in serum antibody levels, supporting their potential for evaluating the therapeutic efficacy. We obtained two epitopes mimetic peptides as advantageous antigens for serodiagnosis and treatment monitoring.

摘要

梅毒是一种多阶段性传播感染疾病,若不治疗会引发严重并发症。由于其蛋白质含量低且体外培养困难,准确诊断仍然具有挑战性。免疫蛋白质组学的进展已鉴定出可提高诊断准确性的关键抗原。利用生物信息学工具设计了免疫显性抗原蛋白Tp0171、Tp0435、Tp0574、Tp0684和Tp0453的表位,并化学合成了模拟肽。进行了一项诊断准确性横断面研究,以验证一种原型技术作为梅毒血清学诊断平台的有效性。在针对梅毒阳性或未感染患者血清样本(n = 122)的基于肽的酶联免疫吸附测定(ELISA)中,使用了五种肽作为抗原。CE0435实现了100%的敏感性和特异性,准确性高。肽CE0171和CE0574表现出高诊断性能,敏感性高于83%,特异性>90%。肽CE0684和CE0453的敏感性分别高于80%和90%;CE0453的特异性降低(约66%)。肽CE0435和CE0171在梅毒各阶段均保持高诊断准确性,敏感性高于83%,特异性超过97%。肽CE0435和CE0171有效地监测了梅毒治疗,血清抗体水平在治疗后显著下降证明了这一点,支持了它们在评估治疗效果方面的潜力。我们获得了两种表位模拟肽,作为血清学诊断和治疗监测的优势抗原。

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