Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia
Corresponding Author
Nancy S. Green
Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA
Correspondence
Nancy S. Green, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
Email: [email protected]
Search for more papers by this authorCaterina Rosano
Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Search for more papers by this authorPaul Bangirana
Department of Psychiatry, Makerere University College of Health Sciences, Kampala, Uganda
Global Health Uganda, Kampala, Uganda
Search for more papers by this authorRobert Opoka
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorDeogratias Munube
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorPhilip Kasirye
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorMichael Kawooya
Department of Radiology, Makerere University College of Health Sciences, Kampala, Uganda
Ernest Cook Ultrasound Research and Education Institute (ECUREI), Mengo Hospital, Kampala, Uganda
Search for more papers by this authorSamson K. Lubowa
Department of Radiology, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorEzekiel Mupere
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorAndrea Conroy
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA
Search for more papers by this authorFrank J. Minja
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
Search for more papers by this authorAmelia K. Boehme
Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA
Search for more papers by this authorMin Suk Kang
Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA
Search for more papers by this authorLawrence S. Honig
Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA
Search for more papers by this authorRichard Idro
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorCorresponding Author
Nancy S. Green
Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA
Correspondence
Nancy S. Green, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
Email: [email protected]
Search for more papers by this authorCaterina Rosano
Department of Epidemiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
Search for more papers by this authorPaul Bangirana
Department of Psychiatry, Makerere University College of Health Sciences, Kampala, Uganda
Global Health Uganda, Kampala, Uganda
Search for more papers by this authorRobert Opoka
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorDeogratias Munube
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorPhilip Kasirye
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorMichael Kawooya
Department of Radiology, Makerere University College of Health Sciences, Kampala, Uganda
Ernest Cook Ultrasound Research and Education Institute (ECUREI), Mengo Hospital, Kampala, Uganda
Search for more papers by this authorSamson K. Lubowa
Department of Radiology, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorEzekiel Mupere
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorAndrea Conroy
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, Indiana, USA
Search for more papers by this authorFrank J. Minja
Department of Radiology and Imaging Sciences, Emory University School of Medicine, Atlanta, Georgia, USA
Search for more papers by this authorAmelia K. Boehme
Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA
Search for more papers by this authorMin Suk Kang
Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA
Search for more papers by this authorLawrence S. Honig
Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA
Search for more papers by this authorRichard Idro
Department of Paediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda
Search for more papers by this authorSummary
Cerebrovascular injury frequently occurs in children with sickle cell anaemia (SCA). Limited access to magnetic resonance imaging and angiography (MRI-MRA) in sub-Saharan Africa impedes detection of clinically unapparent cerebrovascular injury. Blood-based brain biomarkers of cerebral infarcts have been identified in non-SCA adults. Using plasma samples from a well-characterized cross-sectional sample of Ugandan children with SCA, we explored relationships between biomarker levels and MRI-detected cerebral infarcts and transcranial Doppler (TCD) arterial velocity. Testing was performed using a 4-plex panel of brain injury biomarkers, including neurofilament light chain (NfL), a central nervous system neuron-specific protein. Mean biomarker levels from the SCA group (n = 81) were similar to those from non-SCA sibling controls (n = 54). Within the SCA group, NfL levels were significantly higher in those with MRI-detected infarcts compared to no infarcts, and higher with elevated TCD velocity versus normal velocity. Elevated NfL remained strongly associated with MRI-detected infarcts after adjusting for sex and age. All non-SCA controls and SCA participants lacking MRI-detected infarcts had low NfL levels. These data suggest potential utility of plasma-based NfL levels to identify children with SCA cerebrovascular injury. Replication and prospective studies are needed to confirm these novel findings and the clinical utility of NfL versus MRI imaging.
Graphical Abstract
A sample of children with sickle cell anaemia (SCA) and sibling/family controls in Uganda were tested for four blood-based biomarkers. Neurofilament light chain (NfL) strongly correlated with SCA MRI-detected cerebral infarcts.
CONFLICT OF INTEREST STATEMENT
The authors have no relevant conflicts to disclose.
Open Research
DATA AVAILABILITY STATEMENT
Data sharing is available upon request to the corresponding author, except where data access is restricted for protection of the privacy of research participants.
Supporting Information
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