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ORIGINAL RESEARCH article

Front. Immunol.
Sec. NK and Innate Lymphoid Cell Biology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1431066
This article is part of the Research Topic Sepsis Awareness Month 2024 View all articles

Dynamic Changes in Peripheral Blood Lymphocyte Trajectory Predict the Clinical Outcomes of Sepsis

Provisionally accepted
Dongkai Li Dongkai Li Jiahui Zhang Jiahui Zhang Wei Cheng Wei Cheng Guoyu Zhao Guoyu Zhao Xianli Lei Xianli Lei Yawen Xie Yawen Xie Na Cui Na Cui *Hao Wang Hao Wang
  • Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

The final, formatted version of the article will be published soon.

    Background: Sepsis induces profound derangements in the immune system, including lymphopenia, which correlates with immunosuppression and poor prognosis.However, most evaluations of immunosuppression in sepsis patients rely on static, sporadic lymphocyte counts, lacking dynamic modeling over the disease course. This study aimed to apply latent class mixed modeling on longitudinal lymphocyte counts to uncover heterogeneous trajectory phenotypes in sepsis patients and assess their predictive value for clinical outcomes.Results: Four lymphocyte trajectory phenotypes were identified in the retrospective cohort (n=2,149) and externally validated (n=2,388): high-declining (α, 3.8%), stablemedium (β, 69.3%), high-increasing (γ, 3.2%), and stable-low (δ, 23.8%). The α phenotype exhibited the highest disease severity and mortality (25.9%) compared with other phenotypes in both cohorts. In the prospective cohort (n=1,056), all lymphocyte subset counts differed among phenotypes on admission (P < .001) and were lower in non-survivors (P<.05). Multivariable regression demonstrated that age, Acute Physiology and Chronic Health Evaluation-II score, heart rate, natural killer cell count, infection source, and lymphocyte trajectory phenotype were independent predictors of 28-day mortality. A nomogram combining these variables provided individualized risk estimations.The lymphocyte trajectories delineated novel dynamic phenotypes associated with divergent sepsis outcomes. Incorporating longitudinal trajectory modeling and lymphocyte subsets may improve prognostic risk assessment and guide the selection of immunotherapies tailored to specific immune phenotypes in sepsis patients.

    Keywords: Sepsis, Lymphocytes, trajectories, modeling, prognosis

    Received: 11 May 2024; Accepted: 07 Jan 2025.

    Copyright: © 2025 Li, Zhang, Cheng, Zhao, Lei, Xie, Cui and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Na Cui, Department of Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.