Fensterheim Benjamin A, McKeague Michelle, Mathew Divij, Pattekar Ajinkya, Nasta Sean, Kee Macy, Clendenin Cynthia, Martinez Zachary, Diorio Caroline, Greenplate Allison R, Lingappan Krithika, Wherry E John
Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Institute for Immunology and Immune Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
medRxiv. 2025 Sep 5:2025.09.03.25334934. doi: 10.1101/2025.09.03.25334934.
Although inflammatory complications are common in preterm infants, their effects on neonatal immune development remain poorly defined. We therefore investigated whether severe bronchopulmonary dysplasia (BPD) and systemic infection, two major complications of prematurity, produce distinct immune signatures and change immune composition over time. We performed longitudinal high-dimensional immune profiling of residual whole blood from 38 preterm infants sampled every two weeks, along with 10 term infants at birth. Preterm infants with severe BPD showed a progressive increase in Th17-polarized CD4 T cells, neutrophils, and Th17-related cytokines compared to age-matched infants with moderate BPD. In contrast, some preterm infants with systemic bacterial or viral infections mounted robust CD8, CD4, and γδ T cell responses, with oligoclonal expansion, terminal differentiation, and coordinated plasma cytokine shifts that persisted well beyond resolution of infection. These findings demonstrate that different preterm comorbidities imprint the neonatal immune system in divergent ways. Longitudinal immune profiling offers a powerful tool to uncover these trajectories and identify potential targets for intervention.
尽管炎症并发症在早产儿中很常见，但它们对新生儿免疫发育的影响仍不清楚。因此，我们研究了早产的两大主要并发症——重度支气管肺发育不良（BPD）和全身感染——是否会产生不同的免疫特征，并随时间改变免疫组成。我们对38名每两周采样一次的早产儿以及10名足月儿出生时的残留全血进行了纵向高维免疫分析。与年龄匹配的中度BPD婴儿相比，重度BPD早产儿的Th17极化CD4 T细胞、中性粒细胞和Th17相关细胞因子呈渐进性增加。相比之下，一些患有全身性细菌或病毒感染的早产儿表现出强大的CD8、CD4和γδ T细胞反应，伴有寡克隆扩增、终末分化以及血浆细胞因子的协同变化，这些变化在感染消退后仍持续很长时间。这些发现表明，不同的早产合并症以不同的方式影响新生儿免疫系统。纵向免疫分析提供了一个强大的工具来揭示这些轨迹，并确定潜在的干预靶点。
