Novel biomarkers for the early prediction of pediatric cystic echinococcosis post-surgical outcomes

•We identified 59 proteins specific to relapsed patients using comparative proteomics.•Cytoplasmic malate dehydrogenase and citrate synthase are promising early biomarkers.•ELISA using cytoplasmic malate dehydrogenase is the best tool to predict CE outcomes. This study aims to search for reliable serological biomarkers allowing the early prediction of cystic echinococcosis (CE) post-operative outcomes. We applied immunoprecipitation (IP) of Echinococcus granulosus protoscolex antigens with pediatric CE patients' plasma collected at 1-month and 1-year post-surgery, followed by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS). We compared IP proteomic content from relapsed patients within the first-year post-surgery (RCE) to cases with no relapses until 3 post-operative years (NRCE). Selected proteins were recombinantly synthesized and assessed for their prognostic performance by Enzyme-linked immunosorbent assay (ELISA). A total of 305 immunoreactive parasitic proteins were identified, 59 of which were significantly more abundant in RCE than NRCE for both time-points. Four proteins showed the most promising characteristics for predicting CE outcomes: cytoplasmic malate dehydrogenase (Eg-cMDH), citrate synthase (Eg-CS), annexin A6 and severin. ELISA-IgG against the four markers were significantly lower at 1-year post-surgery than 1-month in NRCE, in contrast to RCE that displayed either stable or higher levels. The Eg-cMDH and Eg-CS showed the best prognostic performance, with respective probabilities of being “relapse-free” of 83% and 81%, if a decrease of IgG levels occurred between 1-month and 1-year post-surgery. The Eg-cMDH and Eg-CS are promising biomarkers to predict early CE post-surgical outcomes. [Display omitted]