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Master Thesis

Identification de nouveaux immunomarqueurs du rejet humoral actif en transplantation rénale à travers l’analyse du protéome glomérulaire par spectrométrie de masse

Abstract : Background: issues remain in the diagnosis of antibody-mediated rejection (ABMR) in human kidney transplantation, as the hallmark criteria, the microcirculation inflammation scores and C4d deposits, still lack reproducibility and sensitivity respectively. Methods: we used laser microdissection coupled with tandem mass spectrometry-based proteomics from formalin-fixed and paraffin embedded (FFPE) biopsies to describe the protein profile of antibody-mediated glomerular injuries in human kidney transplantation compared to stable graft controls (SG), and to identify diagnostic biomarkers of active ABMR for daily practice. These latter were secondarily assessed by immunohistochemistry in an independent retrospective cohort of 53 cases by two pathologists. Results: 21 active ABMR and 8 SG were analyzed. We defined a profile of 82 proteins involved in antibodymediated glomerular injuries, marked by evidences of leukocyte activation, cellular stress mediated by the type I and II interferons as well as microcirculation remodeling. We selected three interferon-related endothelial stress proteins for immunohistochemistry: thymidine phosphorylase (TYMP), guanylate-binding protein 1 (GBP1) and tryptophan--tRNA ligase, cytoplasmic (WARS). TYMP and WARS had the best performances for the diagnosis of active ABMR, with a mean sensitivity of 82% and 72%, a mean specificity of 88% and 85%, and a substantial (κ=0,7) and moderate (κ=0,567) agreement respectively. Conclusion: we describe the first glomerular protein profile of ABMR in kidney transplantation from FFPE samples, marked by the interferons environment and microcirculation remodeling. We highlight two relevant immunohistochemical markers, WARS and TYMP, with prima facie good performances in the diagnosis of active ABMR, which now need to be assessed in a prospective larger cohort.
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https://dumas.ccsd.cnrs.fr/dumas-02975174
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Submitted on : Thursday, October 22, 2020 - 2:36:42 PM
Last modification on : Saturday, November 7, 2020 - 3:12:30 AM
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Bertrand Chauveau. Identification de nouveaux immunomarqueurs du rejet humoral actif en transplantation rénale à travers l’analyse du protéome glomérulaire par spectrométrie de masse. Sciences du Vivant [q-bio]. 2020. ⟨dumas-02975174⟩

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