1. Rapid and reliable diagnosis of Wilson disease using X‐ray fluorescence
- Author
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Jean-Charles Duclos-Vallée, Françoise Schmitt, Catherine Guettier, Slavka Kascakova, Tuan Huy Nguyen, Andrea Somogyi, Cameron M. Kewish, Christophe Sandt, Didier Samuel, Joël Poupon, Emmanuel Jacquemin, Dominique Bazin, Bruno Francou, François Le Naour, Stéphan Rouzière, Rodolphe Sobesky, Anne Dubart-Kupperschmitt, Physiopathologie et traitement des maladies du foie, Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Hepatinov (DHU), Université Paris-Sud - Paris 11 (UP11)-Centre Hépato-Biliaire Paul Brousse, Ligne de lumière NANOSCOPIUM, Synchrotron SOLEIL, Laboratoire de Physique des Solides (LPS), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Centre hépato-biliaire (CHB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence pour la maladie de Wilson (CNR wilson), CNR Wilson, Service de Neurologie, Hôpital Lariboisière, Laboratoire de toxicologie biologique [AP-HP], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Ligne de lumière SMIS, Service de Génétique Moléculaire Pharmacogénétique et Hormonologie, Hôpital Bicêtre, Service d’Hépatologie et de Transplantation Hépatique Pédiatriques, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Spectroscopie, Modélisation, Interfaces pour L'Environnement et la Santé (SMiLES), Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Service d’Anatomo-Pathologie [AP-HP], Hôpital Paul Brousse, d'Eggis, Gilles, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
0301 basic medicine ,[SDV.MHEP.AHA] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,Pathology ,medicine.medical_specialty ,Cirrhosis ,diagnosis ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,chemistry.chemical_element ,X-ray fluorescence ,Zinc ,X‐ray fluorescence spectroscopy ,Pathology and Forensic Medicine ,03 medical and health sciences ,0302 clinical medicine ,Cholestasis ,[SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] ,medicine ,Wilson disease ,[SDV.IB] Life Sciences [q-bio]/Bioengineering ,Elemental composition ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Original Articles ,Long evans ,medicine.disease ,Copper ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Paraffin embedded ,3. Good health ,X-ray fluorescence spectroscopy ,030104 developmental biology ,chemistry ,copper ,Original Article ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,030217 neurology & neurosurgery - Abstract
International audience; 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.
- Published
- 2016
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