Putative biomarkers for early diagnosis and prognosis of congenital ocular toxoplasmosis
Thádia Evelyn de Araújo, Luara Isabela dos Santos, Angélica Oliveira Gomes, Ana Carolina Aguiar Vasconcelos Carneiro, Anderson Silva Machado, Jordana Grazziela Alves Coelho-dos-Reis, Vanessa Peruhype-Magalhães, Samantha Ribeiro Béla, Gláucia Manzan Queiroz de Andrade, Daniel Vitor Vasconcelos-Santos, José Nélio Januário, Andréa Teixeira‐Carvalho, Ricardo Wagner Almeida Vítor, Lis Ribeiro do Valle Antonelli, Eloísa Amália Vieira Ferro, Olindo Assis Martins‐Filho, the UFMG Congenital Toxoplasmosis Brazilian Group UFMG-CTBG, beside the authors, Danuza O. Machado Azevedo, Ericka Viana Machado Carellos, Luciana Macedo de Resende, Roberta Maia de Castro Romanelli
Abstract
Abstract 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 CD4 + CD25 + T-cells and T. gondii -specific IFN-γ + CD4 + 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 CD4 + CD25 + 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 IL5 + CD4 + T-cells and IFN-γ + NK-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.