Dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsis
BackgroundSepsis 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 dise...
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Frontiers Media S.A.
2025-02-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1431066/full |
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| author | Dongkai Li Jiahui Zhang Wei Cheng Guoyu Zhao Xianli Lei Yawen Xie Na Cui Hao Wang |
| author_facet | Dongkai Li Jiahui Zhang Wei Cheng Guoyu Zhao Xianli Lei Yawen Xie Na Cui Hao Wang |
| author_sort | Dongkai Li |
| collection | DOAJ |
| description | BackgroundSepsis 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.ResultsFour lymphocyte trajectory phenotypes were identified in the retrospective cohort (n=2,149) and externally validated (n=2,388): high–declining (α, 3.8%), stable–medium (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.ConclusionsThe 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.Clinical trial registrationhttps://www.chictr.org.cn/showproj.aspx?proj=18277, identifier ChiCTR-40 ROC-17010750. |
| format | Article |
| id | doaj-art-99d4822878474300a76c2ead5ee6e860 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-99d4822878474300a76c2ead5ee6e8602025-02-04T06:31:49ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.14310661431066Dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsisDongkai Li0Jiahui Zhang1Wei Cheng2Guoyu Zhao3Xianli Lei4Yawen Xie5Na Cui6Hao Wang7Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Critical Care Medicine, Peking Union Medical College Hospital, Beijing, ChinaDepartment of Critical Care Medicine, Beijing Jishuitan Hospital, Beijing, ChinaBackgroundSepsis 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.ResultsFour lymphocyte trajectory phenotypes were identified in the retrospective cohort (n=2,149) and externally validated (n=2,388): high–declining (α, 3.8%), stable–medium (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.ConclusionsThe 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.Clinical trial registrationhttps://www.chictr.org.cn/showproj.aspx?proj=18277, identifier ChiCTR-40 ROC-17010750.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1431066/fullsepsislymphocytestrajectoriesmodelingprognosis |
| spellingShingle | Dongkai Li Jiahui Zhang Wei Cheng Guoyu Zhao Xianli Lei Yawen Xie Na Cui Hao Wang Dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsis Frontiers in Immunology sepsis lymphocytes trajectories modeling prognosis |
| title | Dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsis |
| title_full | Dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsis |
| title_fullStr | Dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsis |
| title_full_unstemmed | Dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsis |
| title_short | Dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsis |
| title_sort | dynamic changes in peripheral blood lymphocyte trajectory predict the clinical outcomes of sepsis |
| topic | sepsis lymphocytes trajectories modeling prognosis |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1431066/full |
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