Le lundi 22 avril 2024, Madame Justine DEMEUSE, titulaire d'un Master en sciences biomédicales à finalité approfondie et d'un Certificat de formation à la recherche en sciences biomédicales et pharmaceutiques, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences biomédicales et pharmaceutiques, sous la direction de Monsieur Etienne CAVALIER.

Cette épreuve consistera en la défense publique d'une thèse intitulée :

"Initial steps necessary for the standardization of type I collagen-derived bone turnover markers : Characterization of fragments produced during bone resorption by mass spectrometry".

Le jury sera composé de :

Marianne FILLET (Présidente), Caroline LE GOFF (Sercrétaire), Etienne CAVALIER, Pierre DELANAYE, Patrick GARNERO (Univ. Lyon), Baptiste LEROY (UMons), Gabriel MAZZUCHELLI

Résumé de la thèse

This thesis is dedicated to the standardization of CTX immunoassays, which play a crucial role in evaluating bone turnover, particularly in disorders like osteoporosis. CTX, released during bone resorption via cathepsin K activity, encounters discrepancies across commercially available kits, impacting the follow-up of osteoporotic patients. Utilizing an immunopeptidomics approach, we eliminated cross-reactivities as a cause for the observed differences, redirecting attention to the inherent complexity of CTX. Subsequently, high-resolution mass spectrometry was employed to characterize cathepsin K cleavages in type I collagen. This revealed nonspecific cleavages and suggested the presence of multiple CTX species in the bloodstream. A comprehensive workflow was then developed, identifying over 3000 CTX species in plasma and serum. To mitigate species complexity, an optimized multi-enzymatic digestion was employed to reduce the number of CTX species in plasma, facilitating subsequent LC-MS/MS quantitation and thus, reference material production. The methodology expanded to include NTX species due to its analogous structure and release pattern. While promising, further optimization is required for the confident identification of digestion products. Although the formal standardization process has not yet commenced, our research has significantly advanced the understanding of CTX, providing essential information for forthcoming standardization efforts.