Blood-based candidate biomarkers of the presence of neuropsychiatric systemic lupus erythematosus in children.
OBJECTIVE
To examine select brain-reactive proteins for their usefulness to serve as blood-based biomarkers in the screening for neurocognitive deficits in childhood-onset systemic lupus erythematosus (cSLE-NCD).


METHODS
Patients withcSLE (n=40) were studied longitudinally (month 1; month 18): working memory, psychomotor speed and visuoconstructional ability were assessed using formal neurocognitive testing to determine the presence of cSLE-NCD. Patients also completed the computerised Paediatric Automated Neuropsychological Assessment Metrics. The following brain-reactive proteins were measured in the blood: neutrophil gelatinase associated lipocalin (NGAL), S100B, S100A8/9, antibodies to NR2 glutamate receptor (aNR2-AB), ribosomal-P (aP-AB), glycoprotein-1 (aGP1-AB), and lupus anticoagulant.


RESULTS
cSLE-NCD was present in 6 of 40 patients at baseline and 4 of 27 patients with 18-month information. aP-AB positivity was more commonly present with cSLE-NCD than without (p=0.05). aP-ABs were negatively associated with performance on tests assessing working memory, psychomotor speed and visuoconstructional ability in using formal neurocognitive testing. There were also significant negative associations between aP-AB, S100A8/9, aNR2-AB, aGP1-AB, and lupus anticoagulant and accuracy rates on select Paediatric Automated Neuropsychological Assessment Metrics subtests (p<0.05). Over time, decline in cognitive performance was more pronounced among patients with higher NGAL and aNR2-AB levels. Combinations of serum levels of S100A8/9, S100B, NGAL, aNR2-AB and aP-AB were able to identify cSLE-NCD (sensitivity: 100%; specificity 76%) in exploratory analysis.


CONCLUSIONS
Select brain-reactive proteins in the blood are associated with cognitive performance and the presence of cSLE-NCD, cross-sectionally and over time. This raises the possibility that testing of these proteins may assist with the screening of cSLE-NCD.
Department of Pediatrics , University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio , USA ; College of Medicine, University of Cincinnati College of Medicine , Cincinnati, Ohio , USA.
Hermine I
HI
Brunner
Department of Psychiatry and Behavioral Science , Northwestern University Feinberg School of Medicine , Chicago, Illinois , USA.
Marisa S
MS
Klein-Gitelman
Department of Psychiatry and Behavioral Science , Northwestern University Feinberg School of Medicine , Chicago, Illinois , USA ; Department of Child and Adolescent Psychiatry , Ann & Robert H Lurie Children's Hospital of Chicago , Chicago, Illinois , USA.
Frank
F
Zelko
Department of Pediatrics , University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio , USA ; College of Medicine, University of Cincinnati College of Medicine , Cincinnati, Ohio , USA.
Dean W
DW
Beebe
Department of Pediatrics, University of Muenster, Muenster , Germany.
Dirk
D
Foell
College of Medicine, University of Cincinnati College of Medicine , Cincinnati, Ohio , USA ; Department of Internal Medicine , University of Cincinnati College of Medicine , Cincinnati, Ohio , USA.
Jiha
J
Lee
Department of Pediatrics , University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio , USA.
Ahmad
A
Zaal
Department of Pediatrics , University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio , USA ; College of Medicine, University of Cincinnati College of Medicine , Cincinnati, Ohio , USA.
Jordan
J
Jones
Cognitive Science Research Center , University of Oklahoma , Norman, Oklahoma , USA.
Tresa
T
Roebuck-Spencer
Department of Environmental Health , University of Cincinnati College of Medicine , Cincinnati, Ohio , USA.
Jun
J
Ying
Childhood/paediatric lupus; Inflammation; NPSLE; Psychology