Advanced

Biomarkers in the Cerebrospinal Fluid and Neurodegeneration in Langerhans Cell Histiocytosis

Gavhed, Desiree; Akefeldt, Selma Olsson; Osterlundh, Gustaf; Laurencikas, Evaldas; Hjorth, Lars LU ; Blennow, Kaj; Rosengren, Lars and Henter, Jan-Inge (2009) In Pediatric Blood & Cancer2004-01-01+01:00 53(7). p.1264-1270
Abstract
Background. Progressive neurodegeneration may result in potentially severe cognitive and motor dysfunctions as a complication of Langerhans cell histiocytosis (LCH), a suggested IL-17A-associated inflammatory condition. To detect this complication (CNS-LCH) early and to evaluate the potential efficacy of therapeutic interventions, biomarkers detecting and measuring ongoing neurodegeneration Would be valuable. We evaluated cerebrospinal fluid (CSF) biomarkers of ongoing neurodegeneration in CNS-LCH patients. Procedure. Nine patients with endocrine, neuromotor, cognitive or/and behavioral abnormalities as well as neuroradiological evidence of CNS-LCH were evaluated 4-12 years after LCH diagnosis for CSF levels of neurofilament protein light... (More)
Background. Progressive neurodegeneration may result in potentially severe cognitive and motor dysfunctions as a complication of Langerhans cell histiocytosis (LCH), a suggested IL-17A-associated inflammatory condition. To detect this complication (CNS-LCH) early and to evaluate the potential efficacy of therapeutic interventions, biomarkers detecting and measuring ongoing neurodegeneration Would be valuable. We evaluated cerebrospinal fluid (CSF) biomarkers of ongoing neurodegeneration in CNS-LCH patients. Procedure. Nine patients with endocrine, neuromotor, cognitive or/and behavioral abnormalities as well as neuroradiological evidence of CNS-LCH were evaluated 4-12 years after LCH diagnosis for CSF levels of neurofilament protein light chain (NF-L), glial fibrillary acid protein (GFAp), and total tau protein (TAU). Two patients were analyzed longitudinally. One hundred ten children with newly diagnosed acute lymphoblastic leukemia (ALL) served as controls. Results. NF-L, TAU, and GFAp levels were elevated in four, six, and eight of nine patients studied, respectively. NF-L (P < 0.001) and GFAp (P < 0.001) were higher in patients than in controls (TAU not analyzed in controls). The patient with most severe clinical and neuroradiological CNS-LCH displayed the highest levels of NF-L and GFAp whereas three patients without signs of systemic disease had low TAU levels and normal/slightly elevated NF-L. NF-L tended to be higher at radiological progression of neurodegeneration than at Status quo (P = 0.07). Notably, we experienced frequent lumbar puncture complications in these patients. Conclusions. CSF levels of NF-L, TAU, and GFAp appear to be elevated in CNS-LCH. It would be valuable if these markers were validated in order to serve as markers for early CNS-LCH, to monitor disease progression and to evaluate various treatment attempts for CNS-LCH. Pediatr Blood Cancer 2009;53:1264-1270. (C) 2009 Wiley-Liss, Inc. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
histiocytosis, fibrillary acidic protein, glial, cerebrospinal fluid, biomarkers, central nervous system, Langerhans-cell, neurofilament protein, tau proteins
in
Pediatric Blood & Cancer2004-01-01+01:00
volume
53
issue
7
pages
1264 - 1270
publisher
John Wiley and Sons Inc.
external identifiers
  • wos:000271363800017
  • scopus:70449729870
ISSN
1545-5017
DOI
10.1002/pbc.22238
language
English
LU publication?
yes
id
cc0e7529-5a56-4b3a-ba1f-f0b7ad55dee6 (old id 1504821)
date added to LUP
2009-11-25 09:09:40
date last changed
2017-01-01 04:57:06
@article{cc0e7529-5a56-4b3a-ba1f-f0b7ad55dee6,
  abstract     = {Background. Progressive neurodegeneration may result in potentially severe cognitive and motor dysfunctions as a complication of Langerhans cell histiocytosis (LCH), a suggested IL-17A-associated inflammatory condition. To detect this complication (CNS-LCH) early and to evaluate the potential efficacy of therapeutic interventions, biomarkers detecting and measuring ongoing neurodegeneration Would be valuable. We evaluated cerebrospinal fluid (CSF) biomarkers of ongoing neurodegeneration in CNS-LCH patients. Procedure. Nine patients with endocrine, neuromotor, cognitive or/and behavioral abnormalities as well as neuroradiological evidence of CNS-LCH were evaluated 4-12 years after LCH diagnosis for CSF levels of neurofilament protein light chain (NF-L), glial fibrillary acid protein (GFAp), and total tau protein (TAU). Two patients were analyzed longitudinally. One hundred ten children with newly diagnosed acute lymphoblastic leukemia (ALL) served as controls. Results. NF-L, TAU, and GFAp levels were elevated in four, six, and eight of nine patients studied, respectively. NF-L (P &lt; 0.001) and GFAp (P &lt; 0.001) were higher in patients than in controls (TAU not analyzed in controls). The patient with most severe clinical and neuroradiological CNS-LCH displayed the highest levels of NF-L and GFAp whereas three patients without signs of systemic disease had low TAU levels and normal/slightly elevated NF-L. NF-L tended to be higher at radiological progression of neurodegeneration than at Status quo (P = 0.07). Notably, we experienced frequent lumbar puncture complications in these patients. Conclusions. CSF levels of NF-L, TAU, and GFAp appear to be elevated in CNS-LCH. It would be valuable if these markers were validated in order to serve as markers for early CNS-LCH, to monitor disease progression and to evaluate various treatment attempts for CNS-LCH. Pediatr Blood Cancer 2009;53:1264-1270. (C) 2009 Wiley-Liss, Inc.},
  author       = {Gavhed, Desiree and Akefeldt, Selma Olsson and Osterlundh, Gustaf and Laurencikas, Evaldas and Hjorth, Lars and Blennow, Kaj and Rosengren, Lars and Henter, Jan-Inge},
  issn         = {1545-5017},
  keyword      = {histiocytosis,fibrillary acidic protein,glial,cerebrospinal fluid,biomarkers,central nervous system,Langerhans-cell,neurofilament protein,tau proteins},
  language     = {eng},
  number       = {7},
  pages        = {1264--1270},
  publisher    = {John Wiley and Sons Inc.},
  series       = {Pediatric Blood & Cancer2004-01-01+01:00},
  title        = {Biomarkers in the Cerebrospinal Fluid and Neurodegeneration in Langerhans Cell Histiocytosis},
  url          = {http://dx.doi.org/10.1002/pbc.22238},
  volume       = {53},
  year         = {2009},
}