Immuno-epigenetic signature derived in saliva associates with the encephalopathy of prematurity and perinatal inflammatory disorders
Immuno-epigenetic signature derived in saliva associates with the encephalopathy of prematurity and perinatal inflammatory disorders
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唾液中的免疫表观遗传特征与早产儿脑病和围产期炎症性疾病相关
DOI：
10.1101/2022.10.18.22281194
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发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Conole E
中科院分区：
文献类型：
--
作者：
Conole E
研究背景早产与脑发育不良和神经认知功能障碍密切相关，通常称为早产儿脑病（Encephalopathy of Premature，EoP），全身性炎症被认为是其关键驱动因素。来自外周血的炎症的DNA甲基化（DNAm）特征与成人队列中不良的脑成像结果相关。然而，婴儿期DNAm炎症评分的稳健性、其与以炎症为特征的早产合并症的关系、EoP的新生儿神经影像学指标以及唾液跨组织适用性尚不清楚。（n = 155例早产儿，出生时胎龄23.28 - 34.84周，n = 103例足月儿，出生时胎龄37.00 - 42.14周），我们研究了C反应蛋白的DNAm替代物（DNAmCRP）对脑结构和其他临床定义的炎症暴露的影响。我们评估了i）如果DNAm CRP估计值在足月相当年龄的早产儿和足月儿之间存在差异，ii）DNAm CRP如何与不同类型的炎症暴露相关，（母亲，胎儿和出生后）和iii）是否升高的DNAm CRP与新生儿脑容量和白色物质连通性较差的措施。（-0.0107 ± 0.0008，足月儿为-0.0118 ± 0.0006; p < 0.001），以及围产期炎性疾病，包括组织学绒毛膜炎、脓毒症、支气管肺发育不良和坏死性小肠结肠炎（OR范围|两点|到|4.71|，p < 0.01）。具有较高DNAm CRP评分的早产儿在深灰质、白色物质、小脑和杏仁核中的脑体积较低（β范围|0.185|到|0.218|).在足月儿中未观察到此类关联。早产儿中白色物质微结构测量的关联程度最大，其中表观遗传炎症升高与白色物质完整性（β范围）的总体测量较差相关|0.206|到|0.371|），独立于其他混杂exposs.ConclusionsInflammatory-related DNAm捕获早产儿炎症负荷的非稳态负荷。当研究神经发育差异的决定因素时，这种DNAm测量补充了生物学和临床指标。
BackgroundPreterm birth is closely associated with a phenotype that includes brain dysmaturation and neurocognitive impairment, commonly termed Encephalopathy of Prematurity (EoP), of which systemic inflammation is considered a key driver. DNA methylation (DNAm) signatures of inflammation from peripheral blood associate with poor brain imaging outcomes in adult cohorts. However, the robustness of DNAm inflammatory scores in infancy, their relation to comorbidities of preterm birth characterised by inflammation, neonatal neuroimaging metrics of EoP, and saliva cross-tissue applicability are unknown.MethodsUsing salivary DNAm from 258 neonates (n = 155 preterm, gestational age at birth 23.28 – 34.84 weeks, n = 103 term, gestational age at birth 37.00 – 42.14 weeks), we investigated the impact of a DNAm surrogate for C-reactive protein (DNAm CRP) on brain structure and other clinically defined inflammatory exposures. We assessed i) if DNAm CRP estimates varied between preterm infants at term equivalent age and term infants, ii) how DNAm CRP related to different types of inflammatory exposure (maternal, fetal and postnatal) and iii) whether elevated DNAm CRP associated with poorer measures of neonatal brain volume and white matter connectivity.ResultsHigher DNAm CRP was linked to preterm status (-0.0107 ± 0.0008, compared with −0.0118 ± 0.0006 among term infants; p < 0.001), as well as perinatal inflammatory diseases, including histologic chorioamnionitis, sepsis, bronchopulmonary dysplasia, and necrotising enterocolitis (OR range |2.00 | to |4.71|, p < 0.01). Preterm infants with higher DNAm CRP scores had lower brain volume in deep grey matter, white matter, and hippocampi and amygdalae (β range |0.185| to |0.218|). No such associations were observed for term infants. Association magnitudes were largest for measures of white matter microstructure among preterms, where elevated epigenetic inflammation associated with poorer global measures of white matter integrity (β range |0.206| to |0.371|), independent of other confounding exposures.ConclusionsInflammatory-related DNAm captures the allostatic load of inflammatory burden in preterm infants. Such DNAm measures complement biological and clinical metrics when investigating the determinants of neurodevelopmental differences.
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影响因子：
5.1
作者：
Glass, Torin J. A.;Chau, Vann;Miller, Steven P.
通讯作者：
Miller, Steven P.
影响因子：
4.7
作者：
Odintsova VV;Rebattu V;Hagenbeek FA;Pool R;Beck JJ;Ehli EA;van Beijsterveldt CEM;Ligthart L;Willemsen G;de Geus EJC;Hottenga JJ;Boomsma DI;van Dongen J
通讯作者：
van Dongen J
DOI：
10.1001/archpediatrics.2010.20
发表时间：
2010-04-01
影响因子：
--
作者：
Anderson, Peter J.;De Luca, Cinzia R.;Doyle, Lex W.
通讯作者：
Doyle, Lex W.
产前炎症促进产前皮质类固醇诱导的胎儿肺成熟。
影响因子：
8
作者：
Schmidt,AugustoF;Kannan,ParanthamanS;Bridges,James;Presicce,Pietro;Jackson,CourtneyM;Miller,LisaA;Kallapur,SuhasG;Chougnet,ClaireA;Jobe,AlanH
通讯作者：
Jobe,AlanH
影响因子：
9.8
作者：
Andrews, William W.;Cliver, Suzanne P.;Hauth, John C.
通讯作者：
Hauth, John C.