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

  • Eya Ben Salah
    Affiliations
    Département de Biologie clinique B, Faculté de Pharmacie, Laboratoire de Parasitologie-Mycologie Médicale et Moléculaire LR12ES08, Université de Monastir, Monastir, Tunisia

    National French Reference Centre for Echinococcosis, University Hospital, University Bourgogne Franche-Comté, Bd Fleming, Besançon F-25000, France

    Department of Parasitology Mycology, University Hospital of Besançon, UMR/ CNRS 6249 Chrono-Environnement Research Team, University of Bourgogne, Franche-Comté, France
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  • Coralie Barrera
    Affiliations
    National French Reference Centre for Echinococcosis, University Hospital, University Bourgogne Franche-Comté, Bd Fleming, Besançon F-25000, France

    Department of Parasitology Mycology, University Hospital of Besançon, UMR/ CNRS 6249 Chrono-Environnement Research Team, University of Bourgogne, Franche-Comté, France
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  • Wahiba Sakly
    Affiliations
    Département de Biologie clinique B, Faculté de Pharmacie, Laboratoire de Parasitologie-Mycologie Médicale et Moléculaire LR12ES08, Université de Monastir, Monastir, Tunisia
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  • Sana Mosbahi
    Affiliations
    Paediatric Surgery Department, Laboratory of Malformative and Tumor Pathology in Children (LR12SP13), Medical School, Fattouma Bourguiba University Hospital, Monastir, Tunisia
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  • Thierry Balliau
    Affiliations
    PAPPSO, INRAE, CNRS, AgroParisTech, Université Paris-Saclay, GQE-Le Moulon, Gif-sur-Yvette 91190, France
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  • Nathalie Franche
    Affiliations
    Department of Parasitology Mycology, University Hospital of Besançon, UMR/ CNRS 6249 Chrono-Environnement Research Team, University of Bourgogne, Franche-Comté, France
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  • Bruno Gottstein
    Affiliations
    Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Bern, Switzerland
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  • Sabrine Ben Youssef
    Affiliations
    Paediatric Surgery Department, Laboratory of Malformative and Tumor Pathology in Children (LR12SP13), Medical School, Fattouma Bourguiba University Hospital, Monastir, Tunisia
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  • Mongi Mekki
    Affiliations
    Paediatric Surgery Department, Laboratory of Malformative and Tumor Pathology in Children (LR12SP13), Medical School, Fattouma Bourguiba University Hospital, Monastir, Tunisia
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  • Hamouda Babba
    Affiliations
    Département de Biologie clinique B, Faculté de Pharmacie, Laboratoire de Parasitologie-Mycologie Médicale et Moléculaire LR12ES08, Université de Monastir, Monastir, Tunisia
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  • Author Footnotes
    ⁎ Corresponding author at: National French Reference Centre for Echinococcosis, University Hospital, University Bourgogne Franche-Comté, Bd Fleming, Besançon F-25000, France.
    Laurence Millon
    Footnotes
    ⁎ Corresponding author at: National French Reference Centre for Echinococcosis, University Hospital, University Bourgogne Franche-Comté, Bd Fleming, Besançon F-25000, France.
    Affiliations
    National French Reference Centre for Echinococcosis, University Hospital, University Bourgogne Franche-Comté, Bd Fleming, Besançon F-25000, France

    Department of Parasitology Mycology, University Hospital of Besançon, UMR/ CNRS 6249 Chrono-Environnement Research Team, University of Bourgogne, Franche-Comté, France
    Search for articles by this author
  • Author Footnotes
    ⁎ Corresponding author at: National French Reference Centre for Echinococcosis, University Hospital, University Bourgogne Franche-Comté, Bd Fleming, Besançon F-25000, France.
Published:October 03, 2021DOI:https://doi.org/10.1016/j.jinf.2021.09.023

      Highlights

      • 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.

      Summary

      Objective

      This study aims to search for reliable serological biomarkers allowing the early prediction of cystic echinococcosis (CE) post-operative outcomes.

      Methods

      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).

      Results

      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.

      Conclusion

      The Eg-cMDH and Eg-CS are promising biomarkers to predict early CE post-surgical outcomes.

      Graphical abstract

      Keywords

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