Brain, Behavior, and Immunity最新文献

{"title":"Facial cues of sickness reduce trustworthiness judgements, with stronger effects in women","authors":"Megan N. Cesarini-Williams ,&nbsp;Julie Lasselin ,&nbsp;Mats Lekander ,&nbsp;John Axelsson ,&nbsp;Mats J. Olsson ,&nbsp;Arnaud Tognetti","doi":"10.1016/j.bbi.2025.106102","DOIUrl":"10.1016/j.bbi.2025.106102","url":null,"abstract":"<div><div>A behavioral defense against disease involves detecting sickness cues in others and responding adaptively, such as by avoiding social interactions. While studies have shown that humans can discriminate sickness cues above chance in faces after sickness induction, whether this discrimination affects approach-avoidance behaviors remains uncertain. Here, we investigated how facial sickness cues influence judgments of trustworthiness, serving as a proxy measure for social avoidance. In a prior study, facial photographs were taken of 21 individuals when sick (two hours after an endotoxin injection causing a transient systemic inflammation) and healthy (following placebo injection). In the current study, participants in two separate experiments viewed these paired facial photographs and were asked, in a two-alternative forced-choice paradigm, to identify which face appeared sick (n = 94) or more trustworthy (n = 82). Participants discriminated sick faces significantly above chance (73.1 %), with females (76.0 %) performing significantly better than males (69.3 %). Additionally, sick faces were perceived as significantly less trustworthy, being selected in only 34.9 % of trials. Notably, the higher the sickness discrimination accuracy for a particular face, the less likely that face was to be judged as trustworthy. Moreover, females (30.5 %) were significantly less likely than males (39.5 %) to judge sick faces as the more trustworthy looking. Individual differences in participants’ disease vulnerability, disgust sensitivity, and frequency of sickness, as well as facial stimulus participants’ inflammatory response intensity measured via interleukin-6 blood concentrations, body temperature, and sickness symptoms, did not predict sickness discrimination accuracy or trustworthiness judgments. Together, these findings suggest that visual sickness cues negatively affect trustworthiness judgments, potentially reflecting social avoidant behaviors towards individuals who appear sick. While judgments of facial trustworthiness may be considered a social inference about whether an individual is safe to approach, future research should also include manifest measures of approach-avoidance in response to sickness cues.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106102"},"PeriodicalIF":7.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunometabolic biomarkers of brain aging: Nonlinear association between neutrophil-to-HDL cholesterol ratio and cognitive decline in older adults","authors":"Ying Cui","doi":"10.1016/j.bbi.2025.106106","DOIUrl":"10.1016/j.bbi.2025.106106","url":null,"abstract":"<div><h3>Background</h3><div>Immune dysregulation and metabolic disturbances contribute to cognitive decline in aging populations. The neutrophil-to-HDL cholesterol ratio (NHR), an emerging immunometabolic biomarker, reflects systemic inflammation and vascular dysfunction. However, its role in predicting cognitive impairment in older adults remains unclear. This study examined the association between NHR and cognitive impairment, explored non-linear patterns, and compared its predictive performance with conventional biomarkers.</div></div><div><h3>Study Design and Method</h3><div>A total of 2,355 adults aged ≥ 60 years underwent cognitive assessment using standardized neuropsychological tests. Logistic regression evaluated the association between NHR and cognitive impairment, adjusting for demographic, clinical, and lifestyle factors. Restricted cubic splines (RCS) assessed non-linear relationships. Predictive performance was compared using ROC analysis, and machine-learning models were applied to enhance predictive modeling.</div></div><div><h3>Results</h3><div>Higher NHR was significantly associated with cognitive impairment (adjusted OR = 1.14, 95 % CI: 1.01–1.24, <em>P</em> = 0.031). RCS analysis revealed a non-linear relationship (<em>P</em>_{non-linearity} = 0.047), with a threshold effect at NHR = 2.517. The association was stable across subgroups. NHR outperformed traditional biomarkers (AUC = 0.602), and logistic regression achieved the highest accuracy (82.9 %) and F1-score (89.7 %).</div></div><div><h3>Conclusions</h3><div>NHR serves as a potential immunometabolic biomarker for cognitive impairment in older adults, capturing chronic inflammation and metabolic dysfunction linked to brain aging. The observed non-linear pattern suggests a threshold effect, highlighting the importance of early immunometabolic monitoring. These findings support incorporating immunometabolic markers into psychoneuroimmunology-informed risk assessments for cognitive decline.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106106"},"PeriodicalIF":7.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long COVID: Current landscape of neurocognitive sequalae and opportunities to improve care management","authors":"Tiffany A. Walker ,&nbsp;Jonah Z. Kohler ,&nbsp;Michelle M. Haddad","doi":"10.1016/j.bbi.2025.106108","DOIUrl":"10.1016/j.bbi.2025.106108","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106108"},"PeriodicalIF":7.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding NMDAR encephalitis: proteomic markers and computational identification of potential therapeutic pathways","authors":"Shengnan Wang ,&nbsp;Yuhao Yuan ,&nbsp;Xiaoqing Guo ,&nbsp;Mengting Qin ,&nbsp;Jiaojiao Chen ,&nbsp;Dailiang Jiang ,&nbsp;Yuhang Feng ,&nbsp;Ling Mao","doi":"10.1016/j.bbi.2025.106101","DOIUrl":"10.1016/j.bbi.2025.106101","url":null,"abstract":"<div><h3>Background</h3><div>The proteome is a valuable resource for pinpointing therapeutic targets. Therefore, we conducted a proteome-wide Mendelian randomization (MR) study aimed at identifying potential protein markers and therapeutic targets for Anti-N-Methyl-D-Aspartate Receptor Encephalitis (NMDAR-E).</div></div><div><h3>Methods</h3><div>Protein quantitative trait loci (pQTLs) were obtained from seven published genome-wide association studies (GWASs) focusing on the plasma proteome, resulting in summary-level data for 734 circulating protein markers. Genetic associations with NMDAR-E were determined via a large <em>meta</em>-analysis encompassing 323 cases and 1,519 controls. To confirm the causal roles of candidate proteins, we performed sequential colocalization. Subsequently, we experimentally validated prioritized proteins through two complementary approaches: (1) stimulation of HMC3 microglial cells with patient-derived anti-NMDAR-IgG versus control human IgG to assess antibody-induced protein expression dynamics; (2) anti-NMDAR-IgG was stereotactically injected into the lateral ventricle of mice to establish the passive immunization NMDAR-E model, with comparative analysis of lateralized protein expression 7 days post-injection. Additionally, single cell-type expression analysis, protein–protein interaction (PPI) assessments, and evaluations of druggability were conducted to pinpoint enriched cell types and possible therapeutic targets.</div></div><div><h3>Results</h3><div>In total, genetically predicted levels of 37 proteins showed associations with NMDAR-E risk. Elevated levels of three proteins (SIRPA, LGALS3, CASP3) and decreased levels of two proteins (TREM2, IL1RN) were correlated with an increased risk of NMDAR-E. The identified protein-coding genes were predominantly expressed in CD20+ B cells, with comparably elevated expression also observed in mast cells and CD16+ monocytes within the peripheral blood mononuclear cells (PBMCs) of NMDAR-E patients. Anti-NMDAR-IgG induced upregulation of four proteins in human microglial cells and four laterally upregulated proteins in murine brains, with three overlapping responders. Furthermore, proteins TREM2, LGALS3, SIRPA, IL1RN and CASP3, which were initially targeted for drug development in cancer and autoimmune conditions, may also represent therapeutic options for NMDAR-E.</div></div><div><h3>Conclusions</h3><div>This study integrates genetic epidemiology with functional validation, successfully identifying protein biomarkers associated with NMDAR-E risk. The convergence of MR-predicted causal proteins with antibody-driven expression changes in human microglia and mouse models underscores their pathological relevance, providing actionable insights for biomarker screening and therapeutic development.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106101"},"PeriodicalIF":7.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impaired social fear extinction in chronically stressed mice: Impact on inflammatory brain markers and the contribution of oxytocin","authors":"Katharina Gryksa ,&nbsp;Anna K. Schmidtner ,&nbsp;Theresa Schäfer ,&nbsp;Stefan O. Reber ,&nbsp;Inga D. Neumann","doi":"10.1016/j.bbi.2025.106104","DOIUrl":"10.1016/j.bbi.2025.106104","url":null,"abstract":"<div><div>Chronic psychosocial stress is a frequent burden in modern societies and risk factor for numerous somatic and affective disorders, including social anxiety disorder (SAD). Traumatic experiences after prolonged periods of stress exposure often trigger these diseases. Although human and animal studies support the hypothesis of an over-reactive immune system being critically involved in the pathogenesis of psychopathologies, the underlying mechanisms are not fully understood. Accordingly, immune-focused treatment options are lacking.</div><div>The current study was performed in male C57BL/6 and CD1 mice using a combination of chronic subordinate colony housing (CSC), a mouse model for chronic psychosocial stress, and social fear conditioning (SFC), a mouse model for SAD. We can show that CSC prior to SFC exposure facilitates the manifestation of trauma-induced social avoidance and impairs its extinction, while increasing the release of inflammatory factors in the brain, especially in the amygdala. The neuropeptide oxytocin (OXT) with its profound pro-social, stress-buffering and anti-inflammatory effects has been suggested as a promising therapeutic option for stress-related diseases including SAD. Here, we can show that central OXT infusion protected against the observed behavioral phenotype, whereas the inflammatory parameters in the amygdala remained unchanged.</div><div>Although further mechanistic studies are warranted, our findings indicate that chronic psychosocial stress aggravates the development of SAD-like symptoms caused by a traumatic social event and impairs its recovery. In addition, our data provide further evidence for stress- and trauma-protective effects of OXT but did not confirm its anti-inflammatory properties.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106104"},"PeriodicalIF":7.6,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145032785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparing two anti-inflammatory reflexes: Splanchnic and hypothalamic–pituitary–adrenal","authors":"Michael McKinley ,&nbsp;Song T Yao ,&nbsp;Davide Martelli ,&nbsp;Robin McAllen","doi":"10.1016/j.bbi.2025.106099","DOIUrl":"10.1016/j.bbi.2025.106099","url":null,"abstract":"<div><div>Both the autonomic nervous system and the hypothalamic–pituitary–adrenal axis respond to systemic immune challenge by initiating anti-inflammatory reflexes. Here we compare those two homeostatic responses <em>in vivo.</em> We first confirmed in male urethane-anaesthetized rats that disabling the autonomic reflex by bilateral section of the splanchnic sympathetic nerves increased plasma tumor necrosis factor α (TNF) responses to systemic lipopolysaccharide (LPS, 60 µg/kg i.v.) while reducing levels of the key anti-inflammatory cytokine, interleukin 10 (IL-10). Bilateral adrenalectomy, removing both adrenal catecholamines and glucocorticoids, increased TNF responses to LPS by a factor similar to splanchnic nerve section, but unlike splanchnic nerve section, did not reduce IL-10 responses. Both the splanchnic anti-inflammatory reflex and the adrenal glucocorticoid response independently suppress TNF production. When either pathway was disabled individually, TNF responses to LPS increased. When both were disabled simultaneously, by combining adrenalectomy with splanchnic nerve section, TNF levels rose further, in an approximately additive manner. In contrast, IL-10 responses reflected the balance between catecholamine-driven enhancement and glucocorticoid-mediated suppression. When compared to adrenal nerve section, which prevents adrenal catecholamine release, bilateral adrenalectomy (removing both adrenaline and glucocorticoids) actually increased IL-10 responses to LPS. This indicates that circulating glucocorticoids actively suppress IL-10 as well as TNF. That inference was confirmed by restoring plasma corticosterone levels in adrenalectomized rats. We conclude that systemic immune challenge initiates two early, powerful anti-inflammatory reflexes that suppress TNF with similar potency. These reflexes act through independent mechanisms and exert opposing control over IL-10, highlighting their broader regulatory role in cytokine balance.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106099"},"PeriodicalIF":7.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human microglia reduce alpha-synuclein aggregation and are neuroprotective in adult mouse brain","authors":"Katrina Albert ,&nbsp;Sanni Peltonen ,&nbsp;Anni Vanne ,&nbsp;Sara Kälvälä ,&nbsp;Valtteri Syvänen ,&nbsp;Jari Koistinaho ,&nbsp;Kelvin C. Luk ,&nbsp;Šárka Lehtonen","doi":"10.1016/j.bbi.2025.106097","DOIUrl":"10.1016/j.bbi.2025.106097","url":null,"abstract":"<div><div>Microglia, brain-resident immune cells, are involved in pathophysiology of several neurodegenerative diseases, including Parkinson’s disease. Given significant species-specific differences in microglia gene expression, particularly in disease-risk genes, as well as the highly reactive nature of these cells, studying human microglia in a whole brain environment is essential. Here, we established a humanized mouse model by transplanting human induced pluripotent stem cell-derived hematopoietic progenitor cells into the striatum of immunodeficient adult mice and injected human alpha-synuclein preformed fibrils to model Parkinson’s disease pathology. Transplanted human cells engraft, mature into microglia and maintain their phenotype for at least three months post-transplantation. These human microglia interact with alpha-synuclein, significantly limiting its propagation from the striatum to the substantia nigra and further reducing local small aggregates; they also mildly protect tyrosine hydroxylase neurons there. Transcriptomic profiling reveals 56 differentially expressed genes in human microglia in response to alpha-synuclein preformed fibrils, while host mouse cells show 202 gene expression changes, including an upregulation of gene Hcrt (fold change = 7.77, p = 0.0015). Immunohistochemistry analysis further confirms the preservation of hypocretin-positive neurons in the hypothalamus of the transplanted mice (p = 0.0079). The findings highlight the neuroprotective role of human microglia and establish a more disease-relevant <em>in vivo</em> model for investigating alpha-synuclein aggregation and therapeutic interventions in Parkinson’s disease.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106097"},"PeriodicalIF":7.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144996587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The human microglia responsome: a resource for microglia states in health and disease","authors":"Gijsje J.L.J. Snijders ,&nbsp;Katia de Paiva Lopes ,&nbsp;Marjolein A.M. Sneeboer ,&nbsp;Benjamin Z. Muller ,&nbsp;Frederieke A.J. Gigase ,&nbsp;Dante D’Urso ,&nbsp;Ricardo A. Vialle ,&nbsp;Roy Missall ,&nbsp;Raphael Kubler ,&nbsp;Towfique Raj ,&nbsp;Jack Humphrey ,&nbsp;Lot D. de Witte","doi":"10.1016/j.bbi.2025.106095","DOIUrl":"10.1016/j.bbi.2025.106095","url":null,"abstract":"<div><div>Microglia, the immune cells of the brain, are increasingly implicated in neurodegenerative disorders through genetic studies. However, how genetic risk factors for these diseases are related to microglial gene expression, microglial function, and ultimately disease, is still largely unknown. Microglia change rapidly in response to alterations in their cellular environment, which is regulated through changes in transcriptional programs, which are yet poorly understood. Here, we compared the effects of a set of inflammatory and restorative stimuli (lipopolysaccharide, interferon-gamma, resiquimod, tumor necrosis factor-alpha, adenosine triphosphate, dexamethasone, and interleukin-4) on human enriched microglial cells from 67 different donors (N = 398 samples, primarily aged &gt;60 years) at the gene and transcript level. We show that enriched microglia from different anatomical brain regions show distinct responses to inflammatory stimuli. We define specific enriched microglial signatures across conditions which are highly relevant for a wide range of biological functions and complex human diseases. Finally, we used our stimulation signatures to interpret associations from Alzheimer’s disease (AD) (genetic) studies and enriched microglia. Together, we provide a comprehensive transcriptomic resource of the human microglia responsome.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106095"},"PeriodicalIF":7.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microglia-derived exosomes modulate myelin regeneration via activating Nrf2 signaling pathway in oligodendrocyte precursor cells in MS","authors":"Jia-Yi He ,&nbsp;Xiao-Yu Ji ,&nbsp;Bo Huang ,&nbsp;Qing-Qing Sun ,&nbsp;Yao Zhang ,&nbsp;Rui Gao ,&nbsp;Zi-Han Fang ,&nbsp;Li-Bin Wang ,&nbsp;Yan-Hua Li ,&nbsp;Yuan Zhang ,&nbsp;Xing Li","doi":"10.1016/j.bbi.2025.106092","DOIUrl":"10.1016/j.bbi.2025.106092","url":null,"abstract":"<div><div>Demyelination is a prominent feature of multiple sclerosis (MS), where the ability of damaged areas to regenerate myelin is limited. Oligodendrocyte precursor cells (OPCs) accumulate in these areas but struggle to mature into oligodendrocytes (OLGs). Microglia also gather at the lesion site, but their impact on OPCs differentiation is not well understood. Here, we found that miR-155-5p was significantly elevated in the expression profile of exosomes extracted from activated microglia. This miRNA binds to the 3′ UTR of the transcription factor Nrf2 in OPCs, inhibiting their differentiation. In a mouse model of demyelination induced by cuprizone, inhibiting miR-155-5p in microglia led to improved motor function recovery, increased the number of mature oligodendrocytes and promoted remyelination. In this study, we highlight a potential new target for treating demyelinating diseases.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106092"},"PeriodicalIF":7.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144990884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Killer cell immunoglobulin-like receptor (KIR) alleles suggested to be associated with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)","authors":"Donia Jamal Ramadan ,&nbsp;Katherine M. Kichula ,&nbsp;Sudan Tao ,&nbsp;Timothy Porfilio ,&nbsp;Asgeir Lande ,&nbsp;Øystein Fluge ,&nbsp;Olav Mella ,&nbsp;Elin Bolle Strand ,&nbsp;Ola Didrik Saugstad ,&nbsp;Paul J. Norman ,&nbsp;Benedicte A. Lie ,&nbsp;Marte K. Viken","doi":"10.1016/j.bbi.2025.106098","DOIUrl":"10.1016/j.bbi.2025.106098","url":null,"abstract":"<div><div>Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a chronic and debilitating disease with unknown cause. Involvement of infection and immune dysregulation has been suggested, including changes in immune cell subsets and abnormal functions of natural killer (NK) cells. The regulatory NK cell receptors, killer cell immunoglobulin-like receptors (KIR) have previously been investigated in small cohorts of ME/CFS patients with conflicting results regarding gene content. Here, we studied <em>KIR</em> genes also at the allelic level using high-resolution sequencing, in 418 ME/CFS patients and 473 healthy controls. Human leukocyte antigen (HLA) class I genotype data were included for KIR ligand annotation. Our healthy control data represent <em>KIR</em> frequencies for a Norwegian population, which have not previously been reported. We found no association between ME/CFS and <em>KIR</em> gene content or copy number variations. However, our data suggested that specific <em>KIR</em> alleles at loci encoding inhibitory receptors were associated with ME/CFS, which was further supported by allelic haplotype analyses. Three alleles were more frequent in patients, i.e. <em>KIR3DL3*002</em> (OR = 1.43, 95 % CI (1.09–1.86), p = 0.009), <em>KIR3DL1*020</em> (OR = 2.20, 95 % CI (1.19–4.06), p = 0.01) and <em>KIR3DL2*009</em> (OR = 1.56, 95 % CI (1.09–2.23), p = 0.01), while two alleles had a reduced patient frequency, i.e. <em>KIR3DL3*013</em> (OR = 0.60, 95 % CI (0.42–0.86), p = 0.005) and <em>KIR3DL2*</em>010 (OR = 0.46, 95 % CI (0.30–0.71), p = 0.0005). Our data support an involvement of NK cells in ME/CFS.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106098"},"PeriodicalIF":7.6,"publicationDate":"2025-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}