Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy

Paul J. Orchard, Troy Lund, Wes Miller, Steven M. Rothman, Gerald Raymond, David Nascene, Lisa Basso, James Cloyd, Jakub Tolar

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder characterized by the abnormal beta-oxidation of very long chain fatty acids (VLCFA). In 35-40% of children with ALD, an acute inflammatory process occurs in the central nervous system (CNS) leading to demyelination that is rapidly progressive, debilitating and ultimately fatal. Allogeneic hematopoietic stem cell transplantation (HSCT) can halt disease progression in cerebral ALD (C-ALD) if performed early. In contrast, for advanced patients the risk of morbidity and mortality is increased with transplantation. To date there is no means of quantitating neuroinflammation in C-ALD, nor is there an accepted measure to determine prognosis for more advanced patients.Methods: As cellular infiltration has been observed in C-ALD, including activation of monocytes and macrophages, we evaluated the activity of chitotriosidase in the plasma and spinal fluid of boys with active C-ALD. Due to genotypic variations in the chitotriosidase gene, these were also evaluated.Results: We document elevations in chitotriosidase activity in the plasma of patients with C-ALD (n = 38; median activity 1,576 ng/mL/hr) vs. controls (n = 16, median 765 ng/mL/hr, p = 0.0004), and in the CSF of C-ALD patients (n = 38; median activity 4,330 ng/mL/hr) vs. controls (n = 16, median 0 ng/mL/hr, p < 0.0001). In addition, activity levels of plasma and CSF chitotriosidase prior to transplant correlated with progression as determined by the Moser/Raymond functional score 1 year following transplantation (p = 0.002 and < 0.0001, respectively).Conclusions: These findings confirm elevation of chitotriosidase activity in patients with active C-ALD, and suggest that these levels predict prognosis of patients with C-ALD undergoing transplantation.

Original languageEnglish (US)
Article number144
JournalJournal of Neuroinflammation
Volume8
DOIs
StatePublished - Oct 20 2011

Fingerprint

Adrenoleukodystrophy
Biomarkers
Transplantation
Peroxisomal Disorders
Macrophage Activation
Hematopoietic Stem Cell Transplantation
Demyelinating Diseases
Disease Progression
chitotriosidase
Monocytes
Fatty Acids
Central Nervous System
Morbidity
Transplants
Mortality
Genes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Immunology
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Orchard, P. J., Lund, T., Miller, W., Rothman, S. M., Raymond, G., Nascene, D., ... Tolar, J. (2011). Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy. Journal of Neuroinflammation, 8, [144]. https://doi.org/10.1186/1742-2094-8-144
Orchard, Paul J. ; Lund, Troy ; Miller, Wes ; Rothman, Steven M. ; Raymond, Gerald ; Nascene, David ; Basso, Lisa ; Cloyd, James ; Tolar, Jakub. / Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy. In: Journal of Neuroinflammation. 2011 ; Vol. 8.
@article{969bc1114ee543ee9c4b13c1216e22b9,
title = "Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy",
abstract = "Background: Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder characterized by the abnormal beta-oxidation of very long chain fatty acids (VLCFA). In 35-40{\%} of children with ALD, an acute inflammatory process occurs in the central nervous system (CNS) leading to demyelination that is rapidly progressive, debilitating and ultimately fatal. Allogeneic hematopoietic stem cell transplantation (HSCT) can halt disease progression in cerebral ALD (C-ALD) if performed early. In contrast, for advanced patients the risk of morbidity and mortality is increased with transplantation. To date there is no means of quantitating neuroinflammation in C-ALD, nor is there an accepted measure to determine prognosis for more advanced patients.Methods: As cellular infiltration has been observed in C-ALD, including activation of monocytes and macrophages, we evaluated the activity of chitotriosidase in the plasma and spinal fluid of boys with active C-ALD. Due to genotypic variations in the chitotriosidase gene, these were also evaluated.Results: We document elevations in chitotriosidase activity in the plasma of patients with C-ALD (n = 38; median activity 1,576 ng/mL/hr) vs. controls (n = 16, median 765 ng/mL/hr, p = 0.0004), and in the CSF of C-ALD patients (n = 38; median activity 4,330 ng/mL/hr) vs. controls (n = 16, median 0 ng/mL/hr, p < 0.0001). In addition, activity levels of plasma and CSF chitotriosidase prior to transplant correlated with progression as determined by the Moser/Raymond functional score 1 year following transplantation (p = 0.002 and < 0.0001, respectively).Conclusions: These findings confirm elevation of chitotriosidase activity in patients with active C-ALD, and suggest that these levels predict prognosis of patients with C-ALD undergoing transplantation.",
author = "Orchard, {Paul J.} and Troy Lund and Wes Miller and Rothman, {Steven M.} and Gerald Raymond and David Nascene and Lisa Basso and James Cloyd and Jakub Tolar",
year = "2011",
month = "10",
day = "20",
doi = "10.1186/1742-2094-8-144",
language = "English (US)",
volume = "8",
journal = "Journal of Neuroinflammation",
issn = "1742-2094",
publisher = "BioMed Central",

}

Orchard, PJ, Lund, T, Miller, W, Rothman, SM, Raymond, G, Nascene, D, Basso, L, Cloyd, J & Tolar, J 2011, 'Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy', Journal of Neuroinflammation, vol. 8, 144. https://doi.org/10.1186/1742-2094-8-144

Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy. / Orchard, Paul J.; Lund, Troy; Miller, Wes; Rothman, Steven M.; Raymond, Gerald; Nascene, David; Basso, Lisa; Cloyd, James; Tolar, Jakub.

In: Journal of Neuroinflammation, Vol. 8, 144, 20.10.2011.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy

AU - Orchard, Paul J.

AU - Lund, Troy

AU - Miller, Wes

AU - Rothman, Steven M.

AU - Raymond, Gerald

AU - Nascene, David

AU - Basso, Lisa

AU - Cloyd, James

AU - Tolar, Jakub

PY - 2011/10/20

Y1 - 2011/10/20

N2 - Background: Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder characterized by the abnormal beta-oxidation of very long chain fatty acids (VLCFA). In 35-40% of children with ALD, an acute inflammatory process occurs in the central nervous system (CNS) leading to demyelination that is rapidly progressive, debilitating and ultimately fatal. Allogeneic hematopoietic stem cell transplantation (HSCT) can halt disease progression in cerebral ALD (C-ALD) if performed early. In contrast, for advanced patients the risk of morbidity and mortality is increased with transplantation. To date there is no means of quantitating neuroinflammation in C-ALD, nor is there an accepted measure to determine prognosis for more advanced patients.Methods: As cellular infiltration has been observed in C-ALD, including activation of monocytes and macrophages, we evaluated the activity of chitotriosidase in the plasma and spinal fluid of boys with active C-ALD. Due to genotypic variations in the chitotriosidase gene, these were also evaluated.Results: We document elevations in chitotriosidase activity in the plasma of patients with C-ALD (n = 38; median activity 1,576 ng/mL/hr) vs. controls (n = 16, median 765 ng/mL/hr, p = 0.0004), and in the CSF of C-ALD patients (n = 38; median activity 4,330 ng/mL/hr) vs. controls (n = 16, median 0 ng/mL/hr, p < 0.0001). In addition, activity levels of plasma and CSF chitotriosidase prior to transplant correlated with progression as determined by the Moser/Raymond functional score 1 year following transplantation (p = 0.002 and < 0.0001, respectively).Conclusions: These findings confirm elevation of chitotriosidase activity in patients with active C-ALD, and suggest that these levels predict prognosis of patients with C-ALD undergoing transplantation.

AB - Background: Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder characterized by the abnormal beta-oxidation of very long chain fatty acids (VLCFA). In 35-40% of children with ALD, an acute inflammatory process occurs in the central nervous system (CNS) leading to demyelination that is rapidly progressive, debilitating and ultimately fatal. Allogeneic hematopoietic stem cell transplantation (HSCT) can halt disease progression in cerebral ALD (C-ALD) if performed early. In contrast, for advanced patients the risk of morbidity and mortality is increased with transplantation. To date there is no means of quantitating neuroinflammation in C-ALD, nor is there an accepted measure to determine prognosis for more advanced patients.Methods: As cellular infiltration has been observed in C-ALD, including activation of monocytes and macrophages, we evaluated the activity of chitotriosidase in the plasma and spinal fluid of boys with active C-ALD. Due to genotypic variations in the chitotriosidase gene, these were also evaluated.Results: We document elevations in chitotriosidase activity in the plasma of patients with C-ALD (n = 38; median activity 1,576 ng/mL/hr) vs. controls (n = 16, median 765 ng/mL/hr, p = 0.0004), and in the CSF of C-ALD patients (n = 38; median activity 4,330 ng/mL/hr) vs. controls (n = 16, median 0 ng/mL/hr, p < 0.0001). In addition, activity levels of plasma and CSF chitotriosidase prior to transplant correlated with progression as determined by the Moser/Raymond functional score 1 year following transplantation (p = 0.002 and < 0.0001, respectively).Conclusions: These findings confirm elevation of chitotriosidase activity in patients with active C-ALD, and suggest that these levels predict prognosis of patients with C-ALD undergoing transplantation.

UR - http://www.scopus.com/inward/record.url?scp=80054687694&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80054687694&partnerID=8YFLogxK

U2 - 10.1186/1742-2094-8-144

DO - 10.1186/1742-2094-8-144

M3 - Article

AN - SCOPUS:80054687694

VL - 8

JO - Journal of Neuroinflammation

JF - Journal of Neuroinflammation

SN - 1742-2094

M1 - 144

ER -