Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia

Nancy S. Green; Caterina Rosano; Paul Bangirana; Robert Opoka; Deogratias Munube; Philip Kasirye; Michael Kawooya; Samson K. Lubowa; Ezekiel Mupere; Andrea Conroy; Frank J. Minja; Amelia K. Boehme; Min Suk Kang; Lawrence S. Honig; Richard Idro

doi:10.1111/bjh.19036

Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia

Nancy S. Green, Caterina Rosano, Paul Bangirana, Robert Opoka, Deogratias Munube, Philip Kasirye, Michael Kawooya, Samson K. Lubowa, Ezekiel Mupere, Andrea Conroy, Frank J. Minja, Amelia K. Boehme, Min Suk Kang, Lawrence S. Honig, Richard Idro

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	460-467
Number of pages	8
Journal	British Journal of Haematology
Volume	203
Issue number	3
DOIs	https://doi.org/10.1111/bjh.19036
Publication status	Published - Nov 2023
Externally published	Yes

Keywords

Uganda
brain biomarkers
cerebral infarcts
magnetic resonance imaging
sickle cell anaemia

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10.1111/bjh.19036

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Green, N. S., Rosano, C., Bangirana, P., Opoka, R., Munube, D., Kasirye, P., Kawooya, M., Lubowa, S. K., Mupere, E., Conroy, A., Minja, F. J., Boehme, A. K., Kang, M. S., Honig, L. S., & Idro, R. (2023). Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia. British Journal of Haematology, 203(3), 460-467. https://doi.org/10.1111/bjh.19036

@article{68e2c9167193445c8aaa910e0915e4c4,

title = "Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia",

abstract = "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.",

keywords = "Uganda, brain biomarkers, cerebral infarcts, magnetic resonance imaging, sickle cell anaemia",

author = "Green, {Nancy S.} and Caterina Rosano and Paul Bangirana and Robert Opoka and Deogratias Munube and Philip Kasirye and Michael Kawooya and Lubowa, {Samson K.} and Ezekiel Mupere and Andrea Conroy and Minja, {Frank J.} and Boehme, {Amelia K.} and Kang, {Min Suk} and Honig, {Lawrence S.} and Richard Idro",

note = "Publisher Copyright: {\textcopyright} 2023 British Society for Haematology and John Wiley & Sons Ltd.",

year = "2023",

month = nov,

doi = "10.1111/bjh.19036",

language = "English",

volume = "203",

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Green, NS, Rosano, C, Bangirana, P, Opoka, R, Munube, D, Kasirye, P, Kawooya, M, Lubowa, SK, Mupere, E, Conroy, A, Minja, FJ, Boehme, AK, Kang, MS, Honig, LS & Idro, R 2023, 'Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia', British Journal of Haematology, vol. 203, no. 3, pp. 460-467. https://doi.org/10.1111/bjh.19036

TY - JOUR

T1 - Neurofilament light chain

T2 - A potential biomarker for cerebrovascular disease in children with sickle cell anaemia

AU - Green, Nancy S.

AU - Rosano, Caterina

AU - Bangirana, Paul

AU - Opoka, Robert

AU - Munube, Deogratias

AU - Kasirye, Philip

AU - Kawooya, Michael

AU - Lubowa, Samson K.

AU - Mupere, Ezekiel

AU - Conroy, Andrea

AU - Minja, Frank J.

AU - Boehme, Amelia K.

AU - Kang, Min Suk

AU - Honig, Lawrence S.

AU - Idro, Richard

PY - 2023/11

Y1 - 2023/11

N2 - 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.

AB - 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.

KW - Uganda

KW - brain biomarkers

KW - cerebral infarcts

KW - magnetic resonance imaging

KW - sickle cell anaemia

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DO - 10.1111/bjh.19036

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AN - SCOPUS:85168124199

SN - 0007-1048

VL - 203

SP - 460

EP - 467

JO - British Journal of Haematology

JF - British Journal of Haematology

IS - 3

ER -

Neurofilament light chain: A potential biomarker for cerebrovascular disease in children with sickle cell anaemia

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