Biomarkers in the cerebrospinal fluid and neurodegeneration in Langerhans cell histiocytosis.
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.


METHODS
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.
Gavhed
Désirée
D
Department of Woman and Child Health, Childhood Cancer Research Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
Akefeldt
Selma Olsson
SO
Osterlundh
Gustaf
G
Laurencikas
Evaldas
E
Hjorth
Lars
L
Blennow
Kaj
K
Rosengren
Lars
L
Henter
Jan-Inge
JI
D000293:Adolescent; D015415:Biomarkers; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000134:cerebrospinal fluid / Q000209:etiology; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005904:Glial Fibrillary Acidic Protein / Q000134:cerebrospinal fluid*; D006646:Histiocytosis, Langerhans-Cell / Q000134:cerebrospinal fluid* / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007223:Infant; D008297:Male; D009410:Nerve Degeneration; D016900:Neurofilament Proteins / Q000134:cerebrospinal fluid*; D010900:Pituitary Diseases / Q000134:cerebrospinal fluid / Q000209:etiology; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000134:cerebrospinal fluid; D011859:Radiography; D013129:Spinal Puncture / Q000009:adverse effects; D055815:Young Adult; D016875:tau Proteins / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D002556:Cerebrospinal Fluid Proteins; D005904:Glial Fibrillary Acidic Protein; D016900:Neurofilament Proteins; C044882:neurofilament protein L; D016875:tau Proteins