The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas.
The Trypanosoma cruzi Antigen and Epitope Atlas: antibody specificities in Chagas disease patients across the Americas.
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DOI：
10.1038/s41467-023-37522-9
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发表时间：
2023-04-03
影响因子：
16.6
通讯作者：
Aguero, Fernan
中科院分区：
文献类型：
--
作者：
Ricci, Alejandro D.;Bracco, Leonel;Salas-Sarduy, Emir;Ramsey, Janine M.;Nolan, Melissa S.;Lynn, M. Katie;Altcheh, Jaime;Ballering, Griselda E.;Torrico, Faustino;Kesper, Norival;Villar, Juan C.;Marcipar, Ivan S.;Marco, Jorge D.;Aguero, Fernan
在感染期间，免疫系统产生病原体特异性抗体。这些抗体库对感染史具有特异性，并代表了诊断标记的丰富来源。然而，这些抗体的特异性大多是未知的。在这里，我们使用高密度肽阵列检测了恰加斯病患者的人类抗体库。恰加斯病是由克氏锥虫引起的一种被忽视的疾病，克氏锥虫是一种原生动物寄生虫，可逃避免疫介导的消除并引起长期慢性感染。我们描述了对抗原的蛋白质组范围搜索，表征了它们的线性表位，并显示了它们对来自不同人群的71个个体的反应性。通过单残基诱变，我们发现了232个表位的核心功能残基。最后，我们展示了鉴定抗原在挑战性样品上的诊断性能。这些数据集能够以前所未有的深度和粒度研究恰加斯抗体库，同时也提供了丰富的血清学生物标志物来源。这项工作揭示了恰加斯病中人类抗体特异性的多样性和程度，并为诊断和开发这种被忽视的传染病的血清学应用提供了丰富的定义明确的抗原标记。
During an infection the immune system produces pathogen-specific antibodies. These antibody repertoires become specific to the history of infections and represent a rich source of diagnostic markers. However, the specificities of these antibodies are mostly unknown. Here, using high-density peptide arrays we examined the human antibody repertoires of Chagas disease patients. Chagas disease is a neglected disease caused by Trypanosoma cruzi, a protozoan parasite that evades immune mediated elimination and mounts long-lasting chronic infections. We describe a proteome-wide search for antigens, characterised their linear epitopes, and show their reactivity on 71 individuals from diverse human populations. Using single-residue mutagenesis we revealed the core functional residues for 232 of these epitopes. Finally, we show the diagnostic performance of identified antigens on challenging samples. These datasets enable the study of the Chagas antibody repertoire at an unprecedented depth and granularity, while also providing a rich source of serological biomarkers. This work reveals the diversity and extent of human antibody specificities in Chagas disease and provides a wealth of well-defined antigenic markers for diagnosis and development of serological applications for this neglected infectious disease.
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影响因子：
7.3
作者：
Ricci AD;Brunner M;Ramoa D;Carmona SJ;Nielsen M;Agüero F
通讯作者：
Agüero F
影响因子：
3.7
作者：
Bracamonte, Maria E.;Moya Alvarez, Agustin;Marco, Jorge D.
通讯作者：
Marco, Jorge D.
影响因子：
3.7
作者：
Hansen, Lajla Bruntse;Buus, Soren;Schafer-Nielsen, Claus
通讯作者：
Schafer-Nielsen, Claus
影响因子：
3.8
作者：
dos Santos SL;Freitas LM;Lobo FP;Rodrigues-Luiz GF;Mendes TA;Oliveira AC;Andrade LO;Chiari E;Gazzinelli RT;Teixeira SM;Fujiwara RT;Bartholomeu DC
通讯作者：
Bartholomeu DC
影响因子：
3.8
作者：
Granjon, Elodie;Dichtel-Danjoy, Marie-Laure;Zrein, Maan
通讯作者：
Zrein, Maan