Brain, behavior, & immunity - health最新文献

{"title":"Autism and the gut metabolome: Evidence for altered short-chain fatty acid profiles from a systematic review and meta-analysis","authors":"Zhaoming Yang ,&nbsp;Xuemei Chen ,&nbsp;Yinhua Li ,&nbsp;Yanqing Feng ,&nbsp;Liheng Lin ,&nbsp;Xiaohui Hou","doi":"10.1016/j.bbih.2026.101189","DOIUrl":"10.1016/j.bbih.2026.101189","url":null,"abstract":"<div><div>Growing evidence implicates gut microbiome dysbiosis and its metabolites, particularly short-chain fatty acids (SCFAs), in the pathophysiology of autism spectrum disorder (ASD). However, individual study findings are inconsistent.</div></div><div><h3>Objective</h3><div>This systematic review and meta-analysis synthesized evidence comparing SCFA profiles between individuals with ASD and neurotypical controls.</div></div><div><h3>Methods</h3><div>We comprehensively searched PubMed, EMBASE, Cochrane Library, Web of Science, and CNKI databases from inception to December 1, 2024. Observational studies reporting quantitative SCFA measurements were included. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using random-effects models.</div></div><div><h3>Results</h3><div>Sixteen studies (473 ASD cases, 514 controls) were included. Meta-analysis revealed substantial heterogeneity across studies for most SCFAs. Despite this, levels of valeric acid (SMD = 0.76, 95% CI: 0.23 to 1.29) and hexanoic acid (SMD = 0.60, 95% CI: 0.05 to 1.16) were significantly elevated in individuals with ASD. Isobutyric acid also showed a positive association (SMD = 0.21, 95% CI: 0.03 to 0.46) with lower heterogeneity. No significant overall differences were found for acetic, propionic, or butyric acids, but subgroup analyses indicated crucial variations based on sample source (e.g., fecal, plasma, urine).</div></div><div><h3>Conclusion</h3><div>This meta-analysis provides evidence for altered SCFA profiles in ASD, specifically elevated valeric and hexanoic acids and a consistent signal for isobutyric acid, suggesting gut microbial dysbiosis involving distinct metabolic pathways. The significant heterogeneity and sample-source-dependent effects highlight the complexity of the gut-brain axis in ASD and underscore the need for future research with standardized protocols and longitudinal designs to clarify the role of SCFAs.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"53 ","pages":"Article 101189"},"PeriodicalIF":3.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146175539","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral immune system activity in young psychiatry patients","authors":"Lennart Seizer ,&nbsp;Johanna Löchner ,&nbsp;Tobias J. Renner","doi":"10.1016/j.bbih.2025.101143","DOIUrl":"10.1016/j.bbih.2025.101143","url":null,"abstract":"<div><div>The interaction between the immune system and the central nervous system has been implicated in the development of psychiatric disorders in adult patients. However, comprehensive data regarding pediatric psychiatry are still lacking. This study aims to describe the distributions of various markers of immune system activity in a large clinical sample of children and adolescents and summarize the immunological profiles associated with different psychiatric disorders. We analyzed blood samples from 1543 patients aged 6–18 years (62 % female), admitted to the Child and Adolescent Psychiatry at the University Hospital of Tübingen between 2014 and 2024. Immune markers such as C-reactive protein and various cell counts and ratios were measured and regressed on psychiatric diagnoses according to the ICD-10 classification. Our findings revealed several distinct immunological profiles linked to specific psychiatric conditions in youth, such as higher CRP levels in patients with severe stress and adjustment disorders. The study underscores the potential role that immune system aberrations may play in mental health disorders and highlights the importance of investigating this link in this age group. However, some inconsistencies with the existing literature were found, such as the lack of association between depression and immune activity, which calls for further research to elucidate these relationships. Future studies should include longitudinal designs to better understand the causal pathways and potential for immune-targeted therapies in pediatric psychiatry.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101143"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145941060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discrimination exposure and lymphocyte differentiation: Results from the health and retirement study","authors":"Emiko O. Kranz ,&nbsp;Jemar R. Bather ,&nbsp;Xiaoyan Zhang ,&nbsp;Virginia W. Chang ,&nbsp;Steven W. Cole ,&nbsp;Adolfo G. Cuevas","doi":"10.1016/j.bbih.2026.101170","DOIUrl":"10.1016/j.bbih.2026.101170","url":null,"abstract":"<div><div>Everyday discrimination is a social determinant of health linked to disease and mortality, with one potential mechanism of this link involving stress-related signaling that “weathers” immune health. Previous research has examined links between discrimination and inflammatory processes derived from innate immune cells, but little is known about the associations of everyday discrimination with lymphoid lineage cells (T cells and B cells) that mediate adaptive immunity. To better understand the potential immunological impact of everyday discrimination, we analyzed the relationship between Everyday Discrimination Scale scores and flow cytometry data from the Health and Retirement Study (n = 6337; mean age = 70 years, SD = 9 years; 58 % female; 71 % White). Primary analyses adjusted for sociodemographic factors and secondary analyses additionally controlled for health behaviors. Weighted results showed that higher levels of discrimination were significantly associated with higher total CD4⁺ T, CD8⁺ T, and B cell counts. Follow-up analyses of T and B cell maturity indicated a potential link between higher discrimination levels and mature “terminally differentiated” cells, including CD4⁺ TEMRA (7.8 % elevation, 95 % CI: 3.8 %–12.0 % elevation, <em>p</em> &lt; 0.001), CD8⁺ TEMRA (2.9 % elevation, 95 CI: 0.1 %–5.9 % elevation, <em>p</em> = 0.040), and IgD⁻ memory B cells (3.4 % elevation, 95 CI: 0.7 %–6.0 % elevation, <em>p</em> = 0.012), but no significant associations with the immature “naïve” T or B cell subpopulations. Overall, these results suggest that everyday discrimination may contribute to immune aging by promoting the accumulation of terminally differentiated T and B cells, a profile consistent with accelerated immunosenescence in the adaptive immune system.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101170"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145980268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Risk factors, protective factors, peripheral biomarkers, and neurocognitive markers associated with mood disorders: An umbrella review of 103 meta-analyses and systematic reviews” [Brain, Behavior, Immunity Health 48 (2025) 1–27/101068]","authors":"Huixue Wang ,&nbsp;Lijun Ma ,&nbsp;Mi Zhang ,&nbsp;Zhenyue Zu ,&nbsp;Wenzhuo Wei ,&nbsp;Ni Li ,&nbsp;Linxi Yang ,&nbsp;Fenglan Chen ,&nbsp;Chuan Fan ,&nbsp;Kai Wang ,&nbsp;Xiaoming Li","doi":"10.1016/j.bbih.2026.101181","DOIUrl":"10.1016/j.bbih.2026.101181","url":null,"abstract":"","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101181"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147328231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of oral contraceptive use in associations of concussion history with kynurenine pathway metabolites, inflammation, and psychological symptoms in female athletes","authors":"Bryna D. Goeckner ,&nbsp;Jonathan Savitz ,&nbsp;T. Kent Teague ,&nbsp;Benjamin L. Brett ,&nbsp;Adriene M. Beltz ,&nbsp;Timothy B. Meier","doi":"10.1016/j.bbih.2026.101188","DOIUrl":"10.1016/j.bbih.2026.101188","url":null,"abstract":"<div><div>Concussion history is linked to increased risk of psychological symptoms, potentially through inflammation-driven activation of the kynurenine pathway (KP). Use of oral contraceptives (OC) is also associated with increased inflammation, reduced protective kynurenic acid (KynA), and, in some cases, increased psychological symptoms. Despite this evidence and the fact that around half of all female collegiate athletes use OCs, existing research in this area does not account for OC use among female athletes. In this study, we tested the hypothesis that OC use moderates the association of number of prior concussions with serum inflammatory markers and KP metabolites and self-reported psychological symptoms. Collegiate female athletes (N = 69; 30 using OC) participating in a larger cross-sectional study completed semi-structured interviews to retrospectively determine the number of prior concussions (last injury at least 6 months before study enrollment). Linear models assessed associations between the number of prior concussions, OC use, and their interaction with outcomes, controlling for contact-sport exposure. Split analyses tested these associations in athletes using OC versus those not using hormonal contraception (NoHC). Additional exploratory linear models assessed associations between the number of prior concussions, hormonal activity levels of OC, and their interaction on outcomes, controlling for contact-sport exposure. Higher number of prior concussions was associated with elevated quinolinic acid (QuinA), interleukin (IL)-1 receptor antagonist, and psychological symptoms. Although there was no significant interaction, split analyses showed these relationships held only in the NoHC group. Moreover, compared to the NoHC group, OC users exhibited higher C-reactive protein and IL-6 and lower KynA, KynA/QuinA, and KynA/3-hydroxykynurenine. OC formulation moderated biomarker associations in this cohort, with higher progestational and androgenic activity linked to a more proinflammatory profile and greater KP activation with more prior concussions. The results highlight OC use as a potential moderator of the cumulative psychological/immunological effects of repeat concussion in female athletes that should be considered when personalizing treatment for individuals with multiple injuries.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101188"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunoglobulin G complexes from post-infectious ME/CFS, including post-COVID ME/CFS disrupt cellular energetics and alter inflammatory marker secretion","authors":"Zheng Liu ,&nbsp;Claudia Hollmann ,&nbsp;Sharada Kalanidhi ,&nbsp;Stephanie Lamer ,&nbsp;Andreas Schlosser ,&nbsp;Emils Edgars Basens ,&nbsp;Georgy Nikolayshvili ,&nbsp;Liba Sokolovska ,&nbsp;Gabriela Riemekasten ,&nbsp;Rebekka Rust ,&nbsp;Judith Bellmann-Strobl ,&nbsp;Friedemann Paul ,&nbsp;Robert K. Naviaux ,&nbsp;Zaiga Nora-Krukle ,&nbsp;Franziska Sotzny ,&nbsp;Carmen Scheibenbogen ,&nbsp;Bhupesh K. Prusty","doi":"10.1016/j.bbih.2026.101187","DOIUrl":"10.1016/j.bbih.2026.101187","url":null,"abstract":"<div><h3>Background</h3><div>Autoimmunity is a key clinical feature in both post-infectious Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and Post-Acute Sequelae of COVID (PASC). Passive transfer of immunoglobulins from patients' sera into mice induces some clinical features of PASC. However, the physiological effects of immunoglobulins on cellular alterations remain elusive. In this study, we tested the potential effects of immunoglobulins from ME/CFS patients on endothelial cell dysfunction.</div></div><div><h3>Methods</h3><div>We have isolated immunoglobulins from 106 individuals, including ME/CFS (n = 39), PCS-CFS (n = 15), MS (n = 20) patients, and healthy controls (n = 41). Protein composition of the isolated immune complexes was studied using mass spectrometry. The effect of isolated immune complexes on mitochondria was evaluated using confocal microscopy and a Seahorse XFe96 Extracellular Flux Analyzer, and the impact on inflammatory cytokine secretion was studied using a multiplex bead-based assay.</div></div><div><h3>Results</h3><div>Here, we demonstrate that IgG isolated from post-infectious ME/CFS patients selectively induces mitochondrial fragmentation in human endothelial cells and alters cellular energetics. This effect is lost upon cleavage of IgG into its Fab and Fc fragments. The digested Fab fragment from ME/CFS alone was able to alter the cellular energetics, resembling the effect of intact IgG. IgG from post-infectious ME/CFS, including post-COVID ME/CFS patients, induced distinct but separate cytokine secretion profiles in healthy PBMCs. Proteomics analysis of IgG-bound immune complexes revealed significant changes in immune complexes from ME/CFS patients, affecting extracellular matrix organization, whereas those from post-COVID ME/CFS patients pointed to alterations in hemostasis and blood clot regulation.</div></div><div><h3>Conclusions</h3><div>We demonstrate that IgGs from ME/CFS patients carry a chronic protective stress response that promotes mitochondrial adaptation via fragmentation, without altering mitochondrial ATP generation capacity in endothelial cells. Together, these results highlight a potential pathogenic role of IgG in post-infectious ME/CFS and point to novel therapeutic strategies targeting antibody-mediated metabolic dysregulation.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101187"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel epigenetic and transcriptomic profiles of immune, inflammatory, and cellular transduction pathways are associated with chronic perceived stress in midlife women","authors":"Shaimaa Mosad Elrefaay ,&nbsp;Aric A. Prather ,&nbsp;Steven W. Cole ,&nbsp;Elissa Epel ,&nbsp;Kord Kober","doi":"10.1016/j.bbih.2026.101169","DOIUrl":"10.1016/j.bbih.2026.101169","url":null,"abstract":"<div><div>The purpose of this exploratory analysis is to identify pathways common to both DNA methylation and gene expression linked to high perceived stress and evaluate protein-protein interactions of the genes in these pathways. To do this, we selected a sample of premenopausal healthy women stratified for being high (n = 31) and low stress (n = 32) from a large study who had available biospecimens. We used two meta-analysis approaches (strict and inclusive) to identify the pathways supported across the molecular data types, both methylation and gene expression. To delineate potential interactions among the pathways and functional roles of genes linked to the high stress group through epigenomic and transcriptomic analyses, we assessed protein-protein interaction (PPI) network connectivity utilizing the Search Tool for the Retrieval of Interacting Genes (STRING). We identified 17 KEGG pathways that were significant (p-value &lt;0.05) and are implicated in immune response and inflammation, cellular transduction and structure, neurotransmission, and disease. The PPI network exhibits significant interconnectedness among genes, with many gene members of multiple pathways, indicating direct interactions among these pathways. Our findings help target novel stress-related biological pathways for monitoring - for timely intervention, prevention, and tailored treatment approaches. Further replicative studies in wider, diverse populations are necessary to validate the observed functional network pathways and to quantify the specificity of these pathways for duration or magnitude of perceived psychological stress.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101169"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated miRNAs and downstream gene expression associated with poor treatment response in first-episode psychosis","authors":"Shun-Chun Yu ,&nbsp;Yun-Chu Wang ,&nbsp;Hsiu-Ping Lin ,&nbsp;Ya-Wen Jen ,&nbsp;Tzung-Jeng Hwang ,&nbsp;Chih-Min Liu ,&nbsp;Hung-Yu Chan ,&nbsp;Chian-Jue Kuo ,&nbsp;Tsung-Tsair Yang ,&nbsp;Jen-Pang Wang ,&nbsp;Chen-Chung Liu ,&nbsp;Ming H. Hsieh ,&nbsp;Yi-Ting Lin ,&nbsp;Yi-Ling Chien ,&nbsp;Po-Hsiu Kuo ,&nbsp;Ya-Wen Shih ,&nbsp;Sung-Liang Yu ,&nbsp;Hsuan-Yu Chen ,&nbsp;Charlotte Wang ,&nbsp;Wei J. Chen","doi":"10.1016/j.bbih.2026.101190","DOIUrl":"10.1016/j.bbih.2026.101190","url":null,"abstract":"<div><h3>Background</h3><div>Treatment response in first-episode psychosis (FEP) is highly variable, and reliable biomarkers for poor outcomes remain limited. MicroRNAs (miRNAs), important post-transcriptional regulators, have been implicated in psychotic disorders. However, genome-wide miRNA profiling and analyses of their downstream gene networks related to treatment response in FEP remain insufficiently explored.</div></div><div><h3>Methods</h3><div>We analyzed baseline miRNA expression in peripheral blood mononuclear cells from 41 antipsychotic-naïve or minimally treated FEP patients with six-month follow-up. Patients were classified as good (n = 17) or poor responders (n = 24) based on ≥20% symptom improvement on the Positive and Negative Syndrome Scale. Differentially expressed miRNAs were identified by microarray. RNA sequencing was performed to detect candidate target genes, followed by differential expression and functional enrichment analyses.</div></div><div><h3>Results</h3><div>Hsa-miR-34a and hsa-miR-299 were significantly associated with 6-month treatment response. RNA sequencing identified candidate target genes regulated by these miRNAs (704 for hsa-miR-34a and 262 for hsa-miR-299). After multiple-testing correction, three hsa-miR-34a– and five hsa-miR-299–related genes were expressed at higher baseline levels in poor responders than in good responders; their expression levels after 6 months in poor responders remained similar or slightly decreased, whereas in good responders <em>G3BP1</em>, <em>PARD6B</em>, <em>DDHD2</em>, and <em>SLC25A4</em> showed significant reduction and <em>C14orf28</em>, <em>RSBN1</em>, <em>CDC16</em>, and <em>PPM1K</em> showed little or no reduction. These genes are involved in neural development, neural maintenance, and immune response.</div></div><div><h3>Conclusion</h3><div>Our multi-omics approach helps identify miRNAs and their downstream target genes associated with FEP patients’ poor responses to antipsychotics, highlighting potential biomarkers for personalized therapy.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101190"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146189481","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune system up-regulation in securely attached infants during early childhood","authors":"Jorge González-Puelma ,&nbsp;Lindybeth Sarmiento Varón ,&nbsp;Jessica Vidal ,&nbsp;Constanza Ceroni ,&nbsp;Sebastián Escobedo ,&nbsp;Roberto Uribe-Paredes ,&nbsp;David Medina-Ortiz ,&nbsp;Rodrigo A. Cárcamo ,&nbsp;Marcelo A. Navarrete","doi":"10.1016/j.bbih.2026.101184","DOIUrl":"10.1016/j.bbih.2026.101184","url":null,"abstract":"<div><div>Early caregiving relationships shape the coordination of stress and immune systems, yet their biological correlates in early infancy remain insufficiently understood. This study examined whether attachment relationships are associated with mucosal immune function and stress physiology. Thirty-five infants (mean age = 16.6 months) were classified as securely or insecurely attached using the Strange Situation Procedure. Salivary secretory IgA (SIgA) was collected in the morning and afternoon at two time points, and cumulative cortisol was quantified from hair samples.</div><div>Securely attached infants showed higher morning SIgA concentrations and more stable intra-day immune profiles compared with insecurely attached children. No group-level differences were observed for cumulative cortisol, but immune–endocrine associations revealed that higher cortisol was linked to lower morning SIgA and greater intra-day fluctuation. Bayesian regression models supported consistent directional effects, and machine-learning analyses confirmed that SIgA-based features accurately predict attachment type.</div><div>Our findings support the idea that secure attachment fosters stable coordination between immune and endocrine systems during a critical stage of early development. These effects could be readily captured at very early stages of life, identifying SIgA as a potential biomarker of early socioemotional environments. By integrating behavioral, immunological, and computational approaches, this study provides evidence for the biological embedding of attachment and highlights the potential of non-invasive biomarkers to support early identification of psychosocial vulnerability.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101184"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Systemic inflammation and its associations in acute moderate-severe Traumatic Brain Injury: a cross-sectional study","authors":"Lucia M. Li ,&nbsp;Eleftheria Kodosaki ,&nbsp;Chloe J.Y. Xu ,&nbsp;Amanda Heslegrave ,&nbsp;Henrik Zetterberg ,&nbsp;Neil S.N. Graham ,&nbsp;Karl A. Zimmerman ,&nbsp;Elena Garbero ,&nbsp;Federico Moro ,&nbsp;Sandra Magnoni ,&nbsp;Guido Bertolini ,&nbsp;David J. Loane ,&nbsp;David J. Sharp","doi":"10.1016/j.bbih.2026.101179","DOIUrl":"10.1016/j.bbih.2026.101179","url":null,"abstract":"<div><div>Traumatic Brain Injury (TBI) triggers an acute systemic inflammatory response, which may impact outcomes. This response may interact with pre-existing factors linked to inflammation, such as age, to influence outcomes. Previous studies have typically measured few cytokines, but high-dimensional proteomic approaches can sensitively detect a broad range of inflammatory markers, to better characterise post-TBI inflammation.</div><div>We analysed plasma from BIO-AX-TBI study participants (n = 37 acute moderate–severe TBI (Mayo Criteria), n = 22 acute non-TBI trauma (NTT), n = 28 non-injured controls (CON)) using the Alamar NULISA™ panel (&gt;200 inflammatory markers). The NTT group enabled differentiation of TBI-specific versus general injury-related responses. Inflammatory markers were correlated with plasma NFL, GFAP, total tau, UCH-L1 (Simoa®), S100B (Millipore), and subacute (10 days–6 weeks) 3T MRI measures of lesion volume and white matter injury.</div><div>Differential expression analysis identified four markers elevated specifically in TBI (VSNL1, IL1RN/IL-1Ra, GFAP, IKBKG), while other derangements reflected non-specific injury responses. Higher VSNL1 correlated with greater lesion volume (r_s = 0.53) and higher IL1RN/IL-1Ra with greater white matter injury (r_s = −0.66, both FDR-adjusted p &lt; 0.05). IL33, part of the non-specific injury response was higher in participants with good (GOS-E 5–8) versus poor (GOS-E 1–4) outcomes (W = 47, FDR-adjusted p = 0.0024). Using an Elastic Net model trained on healthy controls, we show that “inflammation age” exceeded chronological age in TBI, particularly in younger participants.</div><div>In summary, acute post-TBI inflammation includes both TBI-specific and non-specific components, linked to structural brain injury and functional outcome. Age modulates the inflammatory response. VSNL1, IL1RN/IL-1Ra, and IL33 are potential mediators of post-TBI pathophysiology.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"52 ","pages":"Article 101179"},"PeriodicalIF":3.5,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146038513","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}