Cell adhesion proteins in the cerebrospinal fluid of neonates prenatally exposed to Zika virus: A case–control study
Clara L. Ramos 1, Eduardo C. Nascimento‐Carvalho 1, Gustavo C. Nascimento‐Carvalho 1, Martijn M. VanDuijn 2, Ana‐Luisa Vilas‐Boas 1, Otávio A. Moreno‐Carvalho 3, Lucas P. Carvalho 4, Lona Zeneyedpour 2, Gerben Ferwerda 5, Ronald de Groot 5, Theo M. Luider 2, Cristiana M. Nascimento‐Carvalho 6
1
Bahiana Foundation for Science Development
Bahiana School of Medicine
Salvador
Brazil
2
Department of Neurology
Erasmus MC
Rotterdam
Netherlands
3
Cerebrospinal Fluid Laboratory
José Silveira Foundation
Salvador
Brazil
4
Laboratory of Clinical Research, LAPEC
Gonçalo Moniz Institute
Salvador
Brazil
5
Section of Paediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud Centre for Infectious Diseases
Radboud University Medical Center
Nijmegen
Netherlands
6
Department of Paediatrics
Federal University of Bahia School of Medicine
Salvador
Brazil
Abstract
To compare cell adhesion molecules levels in cerebrospinal fluid (CSF) between Zika virus (ZIKV)‐exposed neonates with/without microcephaly (cases) and controls, 16 neonates (cases), 8 (50%) with and 8 (50%) without microcephaly, who underwent lumbar puncture (LP) during the ZIKV epidemic (2015–2016) were included. All mothers reported ZIKV clinical symptoms during gestation, all neonates presented with congenital infection findings, and other congenital infections were ruled out. Fourteen control neonates underwent LP in the same laboratory (2017–2018). Five cell adhesion proteins were measured in the CSF using mass spectrometry. Neurexin‐1 (3.50 [2.00–4.00] vs. 7.5 [5.00–10.25], P = 0.001), neurexin‐3 (0.00 [0.00–0.00] vs. 3.00 [1.50–4.00], P = 0.001) and neural cell adhesion molecule 2 (NCAM2) (0.00 [0.00–0.75] vs. 1.00 [1.00–2.00], P = 0.001) were significantly lower in microcephalic and non‐microcephalic cases than in controls. When these two sub‐groups of prenatally ZIKA‐exposed children were compared to controls separately, the same results were found. When cases with and without microcephaly were compared, no difference was found. Neurexin‐3 (18.8% vs. 78.6%, P = 0.001) and NCAM2 (25.0% vs. 85.7%, P = 0.001) were less frequently found among the cases. A positive correlation was found between cephalic perimeter and levels of these two proteins. Neurexin‐2 and neurexin‐2b presented no significant differences. Levels of three cell adhesion proteins were significantly lower in CSF of neonates exposed to ZIKV before birth than in controls, irrespective of presence of congenital microcephaly. Moreover, the smaller the cephalic perimeter, the lower CSF cell adhesion protein levels. These findings suggest that low CSF levels of neurexin‐1, neurexin‐3 and NCAM2 may reflect the effects of ZIKV on foetal brain development.
Keywords: cell adhesion protein; cerebrospinal fluid; congenital Zika virus infection; mass spectrometry; microcephaly.
Abbreviations
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