Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4+ T-cell pyroptosis

BackgroundNeutrophil acts as a double-edged sword in the immune system. We hypothesized that an elevated neutrophil granule protein level is associated with sepsis-associated lymphopenia (SAL).MethodsWe enrolled 61 patients with sepsis admitted to the Department of Critical Care Medicine of Peking U...

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Main Authors: Jia-yu Mao, Ya-wen Xie, Xian-li Lei, Jia-hui Zhang, Wei Cheng, Na Cui
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1507800/full
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author Jia-yu Mao
Ya-wen Xie
Xian-li Lei
Jia-hui Zhang
Wei Cheng
Na Cui
author_facet Jia-yu Mao
Ya-wen Xie
Xian-li Lei
Jia-hui Zhang
Wei Cheng
Na Cui
author_sort Jia-yu Mao
collection DOAJ
description BackgroundNeutrophil acts as a double-edged sword in the immune system. We hypothesized that an elevated neutrophil granule protein level is associated with sepsis-associated lymphopenia (SAL).MethodsWe enrolled 61 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between May 2022 and October 2023 in this study. Clinical and immunological parameters were recorded. Levels of neutrophil granule proteins, including myeloperoxidase (MPO) and neutrophil elastase (NE), and pyroptosis factors were examined.ResultsLevels of neutrophil granule proteins (MPO, 82.9 vs. 175.3, p < 0 <.0001; NE, 56.3 vs. 144.2, p < 0.0001) were significantly higher in patients with sepsis with lymphopenia. Neutrophil granule protein levels were independently associated with SAL risk (MPO: OR = 1.0841, 95% CI, 1.0020–1.1730; NE: OR = 1.0540, 95% CI, 1.0040–1.1065). The area under the curve of MPO levels predicting SAL occurrence was 0.939 (95% CI, 0.846–0.984), and that of NE was 0.950 (95% CI, 0.862–0.989). Furthermore, neutrophil granule proteins were significantly correlated with CD4+ T cell and its pyroptosis [MPO and CD4+ T cells (r = −0.4039, p < 0.0001), CD4+NLRP3 (r = 0.4868, p < 0.0001), NE and CD4+ T cells (r = −0.5140, p < 0.0001), and CD4+NLRP3 (r = 0.6513, p < 0.0001)].ConclusionIncreased levels of neutrophil granule proteins were significantly associated with SAL incidence, and a significant relationship between neutrophil granule proteins and the pyroptosis pathway of CD4+ T cells was revealed.Clinical trial registrationchictr.org.cn identifier ChiCTR-ROC-17010750.
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spelling doaj-art-a3111d180a0d49f28efa5374ccc892cc2025-02-07T06:49:37ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15078001507800Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4+ T-cell pyroptosisJia-yu MaoYa-wen XieXian-li LeiJia-hui ZhangWei ChengNa CuiBackgroundNeutrophil acts as a double-edged sword in the immune system. We hypothesized that an elevated neutrophil granule protein level is associated with sepsis-associated lymphopenia (SAL).MethodsWe enrolled 61 patients with sepsis admitted to the Department of Critical Care Medicine of Peking Union Medical College Hospital between May 2022 and October 2023 in this study. Clinical and immunological parameters were recorded. Levels of neutrophil granule proteins, including myeloperoxidase (MPO) and neutrophil elastase (NE), and pyroptosis factors were examined.ResultsLevels of neutrophil granule proteins (MPO, 82.9 vs. 175.3, p < 0 <.0001; NE, 56.3 vs. 144.2, p < 0.0001) were significantly higher in patients with sepsis with lymphopenia. Neutrophil granule protein levels were independently associated with SAL risk (MPO: OR = 1.0841, 95% CI, 1.0020–1.1730; NE: OR = 1.0540, 95% CI, 1.0040–1.1065). The area under the curve of MPO levels predicting SAL occurrence was 0.939 (95% CI, 0.846–0.984), and that of NE was 0.950 (95% CI, 0.862–0.989). Furthermore, neutrophil granule proteins were significantly correlated with CD4+ T cell and its pyroptosis [MPO and CD4+ T cells (r = −0.4039, p < 0.0001), CD4+NLRP3 (r = 0.4868, p < 0.0001), NE and CD4+ T cells (r = −0.5140, p < 0.0001), and CD4+NLRP3 (r = 0.6513, p < 0.0001)].ConclusionIncreased levels of neutrophil granule proteins were significantly associated with SAL incidence, and a significant relationship between neutrophil granule proteins and the pyroptosis pathway of CD4+ T cells was revealed.Clinical trial registrationchictr.org.cn identifier ChiCTR-ROC-17010750.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1507800/fullsepsissepsis-associated lymphopenianeutrophil granule proteinsCD4 lymphocytespyroptosis
spellingShingle Jia-yu Mao
Ya-wen Xie
Xian-li Lei
Jia-hui Zhang
Wei Cheng
Na Cui
Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4+ T-cell pyroptosis
Frontiers in Immunology
sepsis
sepsis-associated lymphopenia
neutrophil granule proteins
CD4 lymphocytes
pyroptosis
title Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4+ T-cell pyroptosis
title_full Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4+ T-cell pyroptosis
title_fullStr Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4+ T-cell pyroptosis
title_full_unstemmed Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4+ T-cell pyroptosis
title_short Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4+ T-cell pyroptosis
title_sort effects of neutrophil granule proteins on sepsis associated lymphopenia and their relationship with cd4 t cell pyroptosis
topic sepsis
sepsis-associated lymphopenia
neutrophil granule proteins
CD4 lymphocytes
pyroptosis
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1507800/full
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