Jennifer C Munoz Pareja, Maria B Mateo Chavez, Julia Alexis Bernal, Kathryn Swaby, Natalie Machado, Charlene Pringle, Kourtney Guthrie, Jennifer Coto, Dhanashree Rajderkar, Joslyn Gober, Juan Solano, Heather J McCrea, Daniel Gonzalez Mosquera, Ayham Alkhachroum, Kristine H O'Phelan, Firas Kobeissy, Robert W Keane, Kevin K Wang, W Dalton Dietrich, Juan Pablo de Rivero Vaccari
{"title":"Association of serum inflammasome proteins and pediatric traumatic brain injury severity.","authors":"Jennifer C Munoz Pareja, Maria B Mateo Chavez, Julia Alexis Bernal, Kathryn Swaby, Natalie Machado, Charlene Pringle, Kourtney Guthrie, Jennifer Coto, Dhanashree Rajderkar, Joslyn Gober, Juan Solano, Heather J McCrea, Daniel Gonzalez Mosquera, Ayham Alkhachroum, Kristine H O'Phelan, Firas Kobeissy, Robert W Keane, Kevin K Wang, W Dalton Dietrich, Juan Pablo de Rivero Vaccari","doi":"10.1038/s41390-025-04410-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pediatric traumatic brain injury (pTBI) often leads to cognitive, behavioral, and motor impairments. NLRP3 inflammasome proteins, such as ASC and caspase-1, may serve as biomarkers for TBI severity due to their role in neuroinflammation. This study aims to assess the association between serum ASC and caspase-1 levels and TBI severity in pediatric patients.</p><p><strong>Methods: </strong>Serum samples were collected at pediatric intensive care unit (ICU) admission (first post-admission), and at 24 and 48 h post-admission, from TBI participants aged 28 days to 18 years and from demographically matched controls. TBI severity was assessed using the Glasgow Coma Scale (GCS).</p><p><strong>Results: </strong>We analyzed samples from 77 pTBI patients and 31 controls. ASC levels were significantly higher across all GCS categories, with the most pronounced differences in the severe category at first post-admission (p = 0.0005, AUROC 0.83) and 24 h post-admission (p < 0.0001, AUROC 0.83). Caspase-1 levels were significantly elevated in the severe category, particularly at first post-admission (p < 0.0001, AUROC 0.85).</p><p><strong>Discussion: </strong>Elevated ASC and caspase-1 levels, especially in severe pTBI cases, suggest their potential as biomarkers for TBI severity. These findings emphasize the role of inflammasome proteins in post-TBI neuroinflammation and support further research into targeted therapies for pediatric TBI.</p><p><strong>Impact: </strong>Increased serum levels of inflammasome proteins ASC and caspase-1 in acute-phase post-admission samples are associated with severe TBI. To our knowledge, this is the first study to examine the inflammasome pathway in pediatric TBI patients across the severity spectrum using serum samples. The study enhances our understanding of NLRP3 inflammasome activation in pediatric TBI by profiling serum levels and examining their clinical correlation with injury severity. It suggests an adjunctive approach to the Glasgow Coma Scale with biomarkers for more precise TBI diagnosis. This research lays the groundwork for future therapeutic strategies targeting inflammasomes in pediatric TBI.</p>","PeriodicalId":19829,"journal":{"name":"Pediatric Research","volume":" ","pages":""},"PeriodicalIF":3.1000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Pediatric Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41390-025-04410-5","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Pediatric traumatic brain injury (pTBI) often leads to cognitive, behavioral, and motor impairments. NLRP3 inflammasome proteins, such as ASC and caspase-1, may serve as biomarkers for TBI severity due to their role in neuroinflammation. This study aims to assess the association between serum ASC and caspase-1 levels and TBI severity in pediatric patients.
Methods: Serum samples were collected at pediatric intensive care unit (ICU) admission (first post-admission), and at 24 and 48 h post-admission, from TBI participants aged 28 days to 18 years and from demographically matched controls. TBI severity was assessed using the Glasgow Coma Scale (GCS).
Results: We analyzed samples from 77 pTBI patients and 31 controls. ASC levels were significantly higher across all GCS categories, with the most pronounced differences in the severe category at first post-admission (p = 0.0005, AUROC 0.83) and 24 h post-admission (p < 0.0001, AUROC 0.83). Caspase-1 levels were significantly elevated in the severe category, particularly at first post-admission (p < 0.0001, AUROC 0.85).
Discussion: Elevated ASC and caspase-1 levels, especially in severe pTBI cases, suggest their potential as biomarkers for TBI severity. These findings emphasize the role of inflammasome proteins in post-TBI neuroinflammation and support further research into targeted therapies for pediatric TBI.
Impact: Increased serum levels of inflammasome proteins ASC and caspase-1 in acute-phase post-admission samples are associated with severe TBI. To our knowledge, this is the first study to examine the inflammasome pathway in pediatric TBI patients across the severity spectrum using serum samples. The study enhances our understanding of NLRP3 inflammasome activation in pediatric TBI by profiling serum levels and examining their clinical correlation with injury severity. It suggests an adjunctive approach to the Glasgow Coma Scale with biomarkers for more precise TBI diagnosis. This research lays the groundwork for future therapeutic strategies targeting inflammasomes in pediatric TBI.
期刊介绍:
Pediatric Research publishes original papers, invited reviews, and commentaries on the etiologies of children''s diseases and
disorders of development, extending from molecular biology to epidemiology. Use of model organisms and in vitro techniques
relevant to developmental biology and medicine are acceptable, as are translational human studies