Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, Brazil.
Programa de Pós-Graduação em Ciências da Saúde: Infectologia e Medicina Tropical, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, 30130-100, Minas Gerais, Brazil; Instituto de Ensino e Pesquisa, Santa Casa de Belo Horizonte. Rua Domingos Vieira, 590, Santa Efigênia, 30150-240, Belo Horizonte, Minas Gerais, Brazil.
Immunol Lett. 2020 Apr;220:11-20. doi: 10.1016/j.imlet.2020.01.005. Epub 2020 Jan 22.
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.
内脏利什曼病(VL)是一种在世界上多个国家存在的高度被忽视的疾病。目前针对这种疾病的治疗方法并不合适,主要是因为药物的毒性和/或高成本。此外,疫苗的开发仍然不足。在这种情况下,迅速进行 VL 诊断是必要的,尽管测试的敏感性和/或特异性值已经存在。在这种情况下,应该确定新的抗原候选物,以更精确地诊断犬和人内脏利什曼病。有鉴于此,本研究评估了重组利什曼原虫吡哆醛激酶(PK)蛋白(rPK)及其衍生的一个特定 B 细胞表位作为诊断标记物的诊断功效。在 ELISA 试验中,结果表明抗原对犬和人血清中 VL 的识别非常敏感,与 VL 相关疾病样本的反应性较低。作为对照的重组 A2(rA2)蛋白和 L. infantum 抗原制剂(SLA)也被证明对有症状病例的检测非常敏感,尽管对无症状血清进行分析时发现敏感性较低。当这些抗原用于评估与 VL 相关的疾病样本时,还发现了高度的交叉反应性。治疗后的血清学随访表明,治疗后 rPK 和抗肽 IgG 抗体水平显著下降。相比之下,在治疗后仍检测到高水平的抗 rA2 和抗 SLA 抗体。总之,rPK 及其特定的 B 细胞表位应被视为犬和人内脏利什曼病的未来研究的诊断标记物。