关键词: cell adhesion protein cerebrospinal fluid congenital Zika virus infection mass spectrometry microcephaly

Mesh : Infant, Newborn Pregnancy Female Child Humans Zika Virus Zika Virus Infection / diagnosis epidemiology Microcephaly / epidemiology Case-Control Studies Cell Adhesion Pregnancy Complications, Infectious / epidemiology Cell Adhesion Molecules Neural Cell Adhesion Molecules

来  源:   DOI:10.1111/ejn.15851

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.
摘要:
比较寨卡病毒(ZIKV)暴露的有/没有小头症(病例)的新生儿和对照组之间脑脊液(CSF)中的细胞粘附分子水平,16例新生儿(病例),8(50%)和8(50%)没有小头畸形,纳入了在ZIKV流行期间(2015-2016年)接受腰椎穿刺(LP)的患者.所有母亲在妊娠期间报告ZIKV临床症状,所有新生儿都有先天性感染的表现,和其他先天性感染被排除。14例对照新生儿在同一实验室接受LP(2017-2018)。使用质谱法在CSF中测量五种细胞粘附蛋白。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)和神经细胞粘附分子2(NCAM2)(0.00[0.00-0.75]vs.1.00[1.00-2.00],P=0.001)在小脑和非小脑病例中明显低于对照组。当产前暴露于ZIKA的儿童的这两个亚组分别与对照组进行比较时,发现了同样的结果。当比较有和没有小头畸形的病例时,没有发现差异。Neurexin-3(18.8%与78.6%,P=0.001)和NCAM2(25.0%vs.85.7%,P=0.001)在病例中发现的频率较低。头部周长与这两种蛋白质的水平之间存在正相关。Neurexin-2和Neurexin-2b没有显着差异。出生前暴露于ZIKV的新生儿CSF中三种细胞粘附蛋白的水平明显低于对照组。无论是否存在先天性小头畸形。此外,头部周长越小,CSF细胞粘附蛋白水平较低。这些发现表明,低CSF水平的neurexin-1,neurexin-3和NCAM2可能反映了ZIKV对胎儿大脑发育的影响。
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