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Evaluation of Leishmania infantum pyridoxal kinase protein for the diagnosis of human and canine visceral leishmaniasis.
Immunology Letters ( IF 4.4 ) Pub Date : 2020-01-22 , DOI: 10.1016/j.imlet.2020.01.005
João A Oliveira-da-Silva 1 , Amanda S Machado 2 , Fernanda F Ramos 1 , Grasiele S V Tavares 1 , Daniela P Lage 1 , Fernanda Ludolf 1 , Bethina T Steiner 3 , Thiago A R Reis 1 , Thaís T O Santos 1 , Lourena E Costa 1 , Vívian T Martins 1 , Nathália C Galvani 1 , Ana T Chaves 1 , Jamil S Oliveira 4 , Miguel A Chávez-Fumagalli 5 , Danielle F de Magalhães-Soares 6 , Mariana C Duarte 1 , Daniel Menezes-Souza 1 , Julia A G Silveira 7 , Ricardo L F Moreira 8 , Ricardo A Machado-de-Ávila 3 , Unaí Tupinambás 1 , Denise U Gonçalves 1 , Eduardo A F Coelho 1
Affiliation  

Visceral leishmaniasis (VL) is a highly neglected disease that is present in several countries worldwide. Present-day treatments against this disease are unsuitable, mainly due to the toxicity and/or high cost of drugs. In addition, the development of vaccines is still insufficient. In this scenario, a prompt VL diagnosis was deemed necessary, although sensitivity and/or specificity values of the tests have been. In this context, new antigenic candidates should be identified to be employed in a more precise diagnosis of canine and human VL. In this light, the present study evaluated the diagnostic efficacy of the Leishmania infantum pyridoxal kinase (PK) protein, applied in its recombinant version (rPK). In addition, one specific B-cell epitope derived of the PK sequence was predicted, synthetized, and evaluated as diagnostic marker. Results in ELISA tests showed that the antigens were highly sensitive to VL identification in dogs and human sera, presenting a low reactivity with VL-related disease samples. The recombinant A2 (rA2) protein and L. infantum antigenic preparation (SLA), used as controls, also proved to be highly sensitive in detecting symptomatic cases, although a low sensitivity was found when asymptomatic sera were analyzed. High cross-reactivity was also found when these antigens were evaluated against VL-related disease samples. The post-therapeutic serological follow-up showed that anti-rPK and anti-peptide IgG antibody levels decreased in significant levels after treatment. By contrast, the presence of high levels of the anti-rA2 and anti-SLA antibodies was still detected after therapy. In conclusion, rPK and its specific B-cell epitope should be considered for future studies as a diagnostic marker for canine and human VL.

中文翻译:

评价婴儿利什曼原虫吡pyr醛激酶蛋白对人和犬内脏利什曼病的诊断。

内脏利什曼病(VL)是一种高度被忽视的疾病,在全球多个国家中都存在。目前针对这种疾病的治疗是不合适的,主要是由于药物的毒性和/或高成本。另外,疫苗的开发仍然不足。在这种情况下,尽管已经进行了检测的敏感性和/或特异性值,但认为必须进行迅速的VL诊断。在这种情况下,应确定新的抗原候选物可用于犬和人VL的更精确诊断。有鉴于此,本研究评估了重组重组版(rPK)中应用的婴儿利什曼原虫吡ido醛激酶(PK)蛋白的诊断功效。此外,预测,合成和评估了一种源自PK序列的特定B细胞表位,并将其作为诊断标记。ELISA测试的结果表明,该抗原对犬和人血清中的VL鉴定高度敏感,与VL相关疾病样品的反应性较低。重组A2(rA2)蛋白和婴儿乳杆菌抗原制剂(SLA)用作对照,在分析有症状病例时也被证明是高度敏感的,尽管分析无症状血清时发现敏感性较低。当这些抗原针对VL相关疾病样本进行评估时,也发现了高交叉反应性。治疗后的血清学随访结果显示,治疗后抗rPK和抗肽IgG抗体水平显着降低。相比之下,治疗后仍检测到高水平的抗rA2和抗SLA抗体。结论,
更新日期:2020-01-22
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