Peripheral immune profiling identifies developmental immune displacement into an HLA-DR-low monocyte state in necrotizing enterocolitis.

Authors

Yihuang Huang, Luyang Hong, Xinhui Guo, Huiyu Chen, Ningxin Luo, Shujuan Li, Junyan Han, Xincheng Cao, Siyuan Jiang, Yun Cao

Published in

Frontiers in immunology. Volume 17. Pages 1868823. Epub Jul 21, 2026.

Abstract

Necrotizing enterocolitis (NEC) is a devastating inflammatory disease of prematurity, yet how it reshapes systemic immunity relative to normal postnatal immune maturation remains unclear. We sought to define the peripheral immune architecture of NEC within a developmental framework and to evaluate whether its dominant signal could be linked to intestinal pathology.
We performed high-dimensional Cytometry by Time-of-Flight profiling on 45 peripheral blood samples from 40 preterm infants spanning birth, postnatal control, pre-onset NEC, NEC onset, and post-onset NEC. Peripheral immune states were modeled relative to a birth-to-postnatal developmental reference trajectory. Key findings were further examined in publicly available intestinal single-cell and bulk transcriptomic datasets, and monocyte human leukocyte antigen-DR (HLA-DR) intensity was assessed as a simplified protein-level metric.
Twenty-seven immune cell subtypes were resolved across major lymphoid and myeloid compartments. In controls, peripheral immunity followed a stereotyped transition from early myeloid predominance toward lymphoid expansion after birth. NEC onset was associated with marked deviation from this trajectory and was dominated by expansion of HLA-DR-low CD16-negative monocytes, contraction of naive and regulatory T-cell subsets, and rewiring of immune correlations toward a myeloid-centered network. Cross-platform analyses supported concordance between the peripheral HLA-DR-low monocyte signal and inflammatory intestinal myeloid states with reduced antigen-presentation programs. Lower monocyte HLA-DR correlated with inflammatory severity; an exploratory within-cohort ROC analysis yielded an area under the curve of 0.84 (95% confidence interval 0.65-0.99).
NEC is associated with developmentally discordant systemic immune remodeling centered on an HLA-DR-low monocyte state in blood, with concordant intestinal myeloid signatures in independent datasets. Monocyte HLA-DR may serve as a mechanistically anchored candidate readout for immune monitoring in preterm infants with NEC, pending external validation.

PMID:
42553378
Bibliographic data and abstract were imported from PubMed on 05 Aug 2026.

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