Instituto de Ciências Biomédicas, Universidade Federal de Uberlândia, Avenida João Naves de Ávila 2121, Santa Mônica, Uberlândia, MG, 38408-100, Brazil.
Instituto René Rachou, Fundação Oswaldo Cruz, Avenida Augusto de Lima, 1715, Barro Preto, Belo Horizonte, MG, 30190-002, Brazil.
Sci Rep. 2020 Oct 7;10(1):16757. doi: 10.1038/s41598-020-73265-z.
In the present study we have evaluated the performance of several immunological biomarkers for early diagnosis and prognosis of congenital toxoplasmosis. Our results showed that ex vivo serum levels of CXCL9, and the frequencies of circulating CD4CD25 T-cells and T. gondii-specific IFN-γCD4 T-cells measured 30-45 days after birth presented high accuracy to distinguish T. gondii-infected infants from healthy age-matched controls (Global Accuracy/AUC = 0.9; 0.9 and 0.8, respectively). Of note was the enhanced performance (Accuracy = 96%) achieved by using a combined stepwise analysis of CD4CD25 T-cells and CXCL9. In addition, high global accuracy (AUC = 0.9) with elevated sensitivity (Se = 98%) was also reached by using the total frequency of in vitro IFN-γ-producing T. gondii-specific T-cells (∑ IFN-γ CD4 & CD8) as a biomarker of congenital toxoplasmosis. Furthermore, the analysis of in vitro T. gondii-specific IL5CD4 T-cells and IFN-γNK-cells displayed a high accuracy for early prognosis of ocular lesion in infant with congenital toxoplasmosis (Global Accuracy/AUC = 0.8 and 0.9, respectively). Together, these findings support the relevance of employing the elements of the cell-mediated immune response as biomarkers with potential to endorse early diagnosis and prognosis of congenital ocular toxoplasmosis to contribute for a precise clinical management and effective therapeutic intervention.
在本研究中,我们评估了几种免疫生物标志物在先天性弓形虫病的早期诊断和预后中的性能。我们的结果表明,出生后 30-45 天测量的体外血清 CXCL9 水平以及循环 CD4CD25 T 细胞和弓形虫特异性 IFN-γCD4 T 细胞的频率,具有很高的准确性,可以区分弓形虫感染的婴儿和健康的同龄对照(总体准确性/AUC=0.9;0.9 和 0.8)。值得注意的是,通过对 CD4CD25 T 细胞和 CXCL9 进行联合逐步分析,可以提高性能(准确性=96%)。此外,使用体外 IFN-γ 产生的弓形虫特异性 T 细胞(∑IFN-γ CD4 和 CD8)的总频率作为先天性弓形虫病的生物标志物,也可以达到很高的总体准确性(AUC=0.9),同时具有较高的灵敏度(Se=98%)。此外,分析体外弓形虫特异性 IL5CD4 T 细胞和 IFN-γNK 细胞,对先天性弓形虫病婴儿眼部病变的早期预后具有很高的准确性(总体准确性/AUC=0.8 和 0.9)。综上所述,这些发现支持将细胞介导的免疫反应作为生物标志物用于早期诊断和预后先天性眼部弓形虫病的相关性,有助于进行精确的临床管理和有效的治疗干预。