Response to Cysteamine in Osteoclasts Obtained from Patients with Nephropathic Cystinosis: A Genotype/Phenotype Correlation
Thomas Quinaux,
Aurélia Bertholet-Thomas,
Aude Servais,
Olivia Boyer,
Isabelle Vrillon,
Julien Hogan,
Sandrine Lemoine,
Ségolène Gaillard,
Candide Alioli,
Sophie Vasseur,
Cécile Acquaviva,
Olivier Peyruchaud,
Irma Machuca-Gayet,
Justine Bacchetta
Affiliations
Thomas Quinaux
Centre de Référence des Maladies Rénales Rares, Centre de Référence des Maladies Rares du Calcium et du Phosphore, Filières de Santé Maladies Rares OSCAR, ORKID et ERK-Net, Hôpital Femme Mère Enfant, 69500 Bron, France
Aurélia Bertholet-Thomas
Centre de Référence des Maladies Rénales Rares, Centre de Référence des Maladies Rares du Calcium et du Phosphore, Filières de Santé Maladies Rares OSCAR, ORKID et ERK-Net, Hôpital Femme Mère Enfant, 69500 Bron, France
Aude Servais
Service de Néphrologie, Hôpital Necker, 75015 Paris, France
Olivia Boyer
Service de Néphrologie Pédiatrique, Centre de Référence des Maladies Rénales Héréditaires de l’Enfant et de l’Adulte, Hôpital Necker-Enfants Malades, AP-HP, 75015 Paris, France
Isabelle Vrillon
Service de Néphrologie Dialyse et Transplantation Pédiatriques, Hôpital d’Enfants, CHRU de Nancy, 54000 Nancy, France
Julien Hogan
Service de Néphrologie Pédiatrique, APHP, Hôpital Robert Debré, 75019 Paris, France
Sandrine Lemoine
Service de Néphrologie, Dialyse et Hypertension Artérielle, Hôpital Edouard Herriot, 69008 Lyon, France
Ségolène Gaillard
EPICIME-CIC 1407, Département d’Epidémiologie Clinique, Groupement Hospitalier Est, Hospices Civils de Lyon, 69500 Bron, France
Candide Alioli
INSERM 1033 Research Unit, 69008 Lyon, France
Sophie Vasseur
Service de Biochimie et Biologie Moléculaire, Unité Maladies Héréditaires du Métabolisme, Groupement Hospitalier Est, Hospices Civils de Lyon, 69500 Bron, France
Cécile Acquaviva
Service de Biochimie et Biologie Moléculaire, Unité Maladies Héréditaires du Métabolisme, Groupement Hospitalier Est, Hospices Civils de Lyon, 69500 Bron, France
Olivier Peyruchaud
INSERM 1033 Research Unit, 69008 Lyon, France
Irma Machuca-Gayet
INSERM 1033 Research Unit, 69008 Lyon, France
Justine Bacchetta
Centre de Référence des Maladies Rénales Rares, Centre de Référence des Maladies Rares du Calcium et du Phosphore, Filières de Santé Maladies Rares OSCAR, ORKID et ERK-Net, Hôpital Femme Mère Enfant, 69500 Bron, France
Bone complications of cystinosis have been recently described. The main objectives of this paper were to determine in vitro the impact of CTNS mutations and cysteamine therapy on human osteoclasts and to carry out a genotype-phenotype analysis related to osteoclastic differentiation. Human osteoclasts were differentiated from peripheral blood mononuclear cells (PBMCs) and were treated with increasing doses of cysteamine (0, 50, 200 µM) and then assessed for osteoclastic differentiation. Results are presented as median (min-max). A total of 17 patients (mainly pediatric) were included, at a median age of 14 (2–61) years, and a eGFR of 64 (23–149) mL/min/1.73 m2. Most patients (71%) were under conservative kidney management (CKM). The others were kidney transplant recipients. Three functional groups were distinguished for CTNS mutations: cystinosin variant with residual cystin efflux activity (RA, residual activity), inactive cystinosin variant (IP, inactive protein), and absent protein (AP). PBMCs from patients with residual cystinosin activity generate significantly less osteoclasts than those obtained from patients of the other groups. In all groups, cysteamine exerts an inhibitory effect on osteoclastic differentiation at high doses. This study highlights a link between genotype and osteoclastic differentiation, as well as a significant impact of cysteamine therapy on this process in humans.
