Rapid and reliable diagnosis of Wilson disease using X-ray fluorescence

Abstract : Wilson's disease (WD) is a rare autosomal recessive disease due to mutations of the gene encoding the copper-transporter ATP7B. The diagnosis is hampered by the variability of symptoms induced by copper accumulation , the inconstancy of the pathognomonic signs and the absence of a reliable diagnostic test. We investigated the diagnostic potential of X-ray fluorescence (XRF) that allows quantitative analysis of multiple elements. Studies were performed on animal models using Wistar rats (n = 10) and Long Evans Cinnamon (LEC) rats (n = 11), and on human samples including normal livers (n = 10), alcohol cirrhosis (n = 8), haemo-chromatosis (n = 10), cholestasis (n = 6) and WD (n = 22). XRF experiments were first performed using synchrotron radiation to address the elemental composition at the cellular level. High-resolution mapping of tissue sections allowed measurement of the intensity and the distribution of copper, iron and zinc while preserving the morphology. Investigations were further conducted using a laboratory X-ray source for irradiating whole pieces of tissue. The sensitivity of XRF was highlighted by the discrimination of LEC rats from wild type even under a regimen using copper deficient food. XRF on whole formalin-fixed paraffin embedded needle biopsies allowed profiling of the elements in a few minutes. The intensity of copper related to iron and zinc significantly discriminated WD from other genetic or chronic liver diseases with 97.6% specificity and 100% sensitivity. This study established a definite diagnosis of Wilson's disease based on XRF. This rapid and versatile method can be easily implemented in a clinical setting.
Liste complète des métadonnées

Littérature citée [32 références]  Voir  Masquer  Télécharger

https://hal.sorbonne-universite.fr/hal-01333064
Contributeur : Gilles D'Eggis <>
Soumis le : vendredi 17 juin 2016 - 09:37:53
Dernière modification le : vendredi 30 novembre 2018 - 01:27:35
Document(s) archivé(s) le : dimanche 18 septembre 2016 - 10:29:53

Fichier

cjp248 (1).pdf
Publication financée par une institution

Licence


Distributed under a Creative Commons Paternité 4.0 International License

Identifiants

Citation

Slávka Kaščáková, Cameron M. Kewish, Stéphan Rouzière, Françoise Schmitt, Rodolphe Sobesky, et al.. Rapid and reliable diagnosis of Wilson disease using X-ray fluorescence. Journal of Pathology: Clinical Research, Wiley Open Access, 2016, 2 (3), pp.175-186 〈10.1002/cjp2.48〉. 〈hal-01333064〉

Partager

Métriques

Consultations de la notice

376

Téléchargements de fichiers

227