Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy

Acid Ceramidase Deficiency is characterized by a unique plasma cytokine and ceramide profile that is altered by therapy

Author Dworski, Shaalee Google Scholar
Lu, Ping Google Scholar
Khan, Aneal Google Scholar
Maranda, Bruno Google Scholar
Mitchell, John J. Google Scholar
Parini, Rossella Google Scholar
Di Rocco, Maja Google Scholar
Hugle, Boris Google Scholar
Yoshimitsu, Makoto Google Scholar
Magnusson, Bo Google Scholar
Makay, Balahan Google Scholar
Arslan, Nur Google Scholar
Guelbert, Norberto Google Scholar
Ehlert, Karoline Google Scholar
Jarisch, Andrea Google Scholar
Gardner-Medwin, Janet Google Scholar
Dagher, Rawane Google Scholar
Terreri, Maria Teresa Autor UNIFESP Google Scholar
Lorenco, Charles Marques Google Scholar
Barillas-Arias, Lilianna Google Scholar
Tanpaiboon, Pranoot Google Scholar
Solyom, Alexander Google Scholar
Norris, James S. Google Scholar
He, Xingxuan Google Scholar
Schuchman, Edward H. Google Scholar
Levade, Thierry Google Scholar
Medin, Jeffrey A. Google Scholar
Abstract Acid Ceramidase Deficiency (Farber disease, FD) is an ultra-rare Lysosomal Storage Disorder that is poorly understood and often misdiagnosed as Juvenile Idiopathic Arthritis (JIA). Hallmarks of FD are accumulation of ceramides, widespread macrophage infiltration, splenomegaly, and lymphocytosis. The cytokines involved in this abnormal hematopoietic state are unknown. There are dozens of ceramide species and derivatives, but the specific ones that accumulate in FD have not been investigated. We used a multiplex assay to analyze cytokines and mass spectrometry to analyze ceramides in plasma from patients and mice with FD, controls, Farber patients treated by hematopoietic stem cell transplantation (HSCT), JIA patients, and patients with Gaucher disease. KC, MIP-1 alpha, and MCP-1 were sequentially upregulated in plasma from FD mice. MCP-1, IL-10, IL-6, IL-12, and VEGF levels were elevated in plasma from Farber patients but not in control or JIA patients. C16-Ceramide (C16-Cer) and dhC16-Cer were upregulated in plasma from FD mice. a-OH-C18-Cer, dhC12-Cer, dhC24:1-Cer, and C22:1-Cer-1P accumulated in plasma from patients with FD. Most cytokines and only a-OH-C18-Cer returned to baseline levels in HSCT-treated Farber patients. Sphingosines were not altered. Chitotriosidase activity was also relatively low. A unique cytokine and ceramide profile was seen in the plasma of Farber patients that was not observed in plasma from HSCT-treated Farber patients, JIA patients, or Gaucher patients. The cytokine profile can potentially be used to prevent misdiagnosis of Farber as JIA and to monitor the response to treatment. Further understanding of why these signaling molecules and lipids are elevated can lead to better understanding of the etiology and pathophysiology of FD and inform development of future treatments. (C) 2016 Elsevier B.V. All rights reserved.
Keywords Chemokines
Idiopathic Arthritis
xmlui.dri2xhtml.METS-1.0.item-coverage Amsterdam
Language English
Sponsor Rare Disease Foundation
BC Children's Hospital Foundation
National Institutes of Health
Vaincre les Maladies Lysosomales
Plexcera Therapeutics
Grant number NIH: 1R21NS078191-01A1
NIH: R01 DK54830
Date 2017
Published in Biochimica Et Biophysica Acta-Molecular Basis Of Disease. Amsterdam, v. 1863, n. 2, p. 386-394, 2017.
ISSN 0925-4439 (Sherpa/Romeo, impact factor)
Publisher Elsevier Science Bv
Extent 386-394
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000392779800005

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