Jia-Yu Mao, Ya-Wen Xie, Xian-Li Lei, Jia-Hui Zhang, Wei Cheng, Na Cui
{"title":"Effects of neutrophil granule proteins on sepsis-associated lymphopenia and their relationship with CD4<sup>+</sup> T-cell pyroptosis.","authors":"Jia-Yu Mao, Ya-Wen Xie, Xian-Li Lei, Jia-Hui Zhang, Wei Cheng, Na Cui","doi":"10.3389/fimmu.2025.1507800","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Neutrophil 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).</p><p><strong>Methods: </strong>We 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.</p><p><strong>Results: </strong>Levels of neutrophil granule proteins (MPO, 82.9 vs. 175.3, <i>p</i> < 0 <.0001; NE, 56.3 vs. 144.2, <i>p</i> < 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<sup>+</sup> T cell and its pyroptosis [MPO and CD4<sup>+</sup> T cells (<i>r</i> = -0.4039, <i>p</i> < 0.0001), CD4<sup>+</sup>NLRP3 (<i>r</i> = 0.4868, <i>p</i> < 0.0001), NE and CD4<sup>+</sup> T cells (<i>r</i> = -0.5140, <i>p</i> < 0.0001), and CD4<sup>+</sup>NLRP3 (<i>r</i> = 0.6513, <i>p</i> < 0.0001)].</p><p><strong>Conclusion: </strong>Increased 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<sup>+</sup> T cells was revealed.</p><p><strong>Clinical trial registration: </strong>chictr.org.cn identifier ChiCTR-ROC-17010750.</p>","PeriodicalId":12622,"journal":{"name":"Frontiers in Immunology","volume":"16 ","pages":"1507800"},"PeriodicalIF":5.7000,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11842378/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Immunology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fimmu.2025.1507800","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Neutrophil 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).
Methods: We 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.
Results: Levels 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)].
Conclusion: Increased 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.
期刊介绍:
Frontiers in Immunology is a leading journal in its field, publishing rigorously peer-reviewed research across basic, translational and clinical immunology. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to researchers, academics, clinicians and the public worldwide.
Frontiers in Immunology is the official Journal of the International Union of Immunological Societies (IUIS). Encompassing the entire field of Immunology, this journal welcomes papers that investigate basic mechanisms of immune system development and function, with a particular emphasis given to the description of the clinical and immunological phenotype of human immune disorders, and on the definition of their molecular basis.