Pub Date : 2024-09-20DOI: 10.1016/j.bbih.2024.100863
Jeremia J. Pyuza , Marloes M.A.R. van Dorst , Koen Stam , Linda Wammes , Marion König , Vesla I. Kullaya , Yvonne Kruize , Wesley Huisman , Nikuntufya Andongolile , Anastazia Ngowi , Elichilia R. Shao , Alex Mremi , Pancras C.W. Hogendoorn , Sia E. Msuya , Simon P. Jochems , Wouter A.A. de Steenhuijsen Piters , Maria Yazdanbakhsh
Immune system and vaccine responses vary across geographical locations worldwide, not only between high and low-middle income countries (LMICs), but also between rural and urban populations within the same country. Lifestyle factors such as housing conditions, exposure to microorganisms and parasites and diet are associated with rural-and urban-living. However, the relationships between these lifestyle factors and immune profiles have not been mapped in detail. Here, we profiled the immune system of 100 healthy Tanzanians living across four rural/urban areas using mass cytometry. We developed a lifestyle score based on an individual's household assets, housing condition and recent dietary history and studied the association with cellular immune profiles. Seventeen out of 80 immune cell clusters were associated with living location or lifestyle score, with eight identifiable only using lifestyle score. Individuals with low lifestyle score, most of whom live in rural settings, showed higher frequencies of NK cells, plasmablasts, atypical memory B cells, T helper 2 cells, regulatory T cells and activated CD4+ T effector memory cells expressing CD38, HLA-DR and CTLA-4. In contrast, those with high lifestyle score, most of whom live in urban areas, showed a less activated state of the immune system illustrated by higher frequencies of naïve CD8+ T cells. Using an elastic net machine learning model, we identified cellular immune signatures most associated with lifestyle score. Assuming a link between these immune profiles and vaccine responses, these signatures may inform us on the cellular mechanisms underlying poor responses to vaccines, but also reduced autoimmunity and allergies in low- and middle-income countries.
免疫系统和疫苗反应在全球不同地理位置之间存在差异，不仅在高收入国家和中低收入国家之间存在差异，而且在同一国家的农村人口和城市人口之间也存在差异。居住条件、接触微生物和寄生虫的机会以及饮食等生活方式因素与农村和城市生活息息相关。然而，这些生活方式因素与免疫特征之间的关系还没有被详细描述。在这里，我们使用质谱细胞计数法对生活在四个城乡结合部的 100 名健康坦桑尼亚人的免疫系统进行了分析。我们根据个人的家庭资产、住房条件和最近的饮食史制定了生活方式评分，并研究了其与细胞免疫特征的关联。在 80 个免疫细胞群中，有 17 个与居住地点或生活方式评分有关，其中有 8 个只能通过生活方式评分来识别。生活方式得分低的人大多数生活在农村，他们的 NK 细胞、浆细胞、非典型记忆 B 细胞、T 辅助 2 细胞、调节性 T 细胞和表达 CD38、HLA-DR 和 CTLA-4 的活化 CD4+ T 效应记忆细胞的频率较高。与此相反，生活方式得分高的人，其中大多数生活在城市地区，其免疫系统的激活状态较差，表现为幼稚的 CD8+ T 细胞频率较高。利用弹性网机器学习模型，我们确定了与生活方式得分最相关的细胞免疫特征。假设这些免疫特征与疫苗反应之间存在联系，那么这些特征可能会让我们了解疫苗反应不佳的细胞机制，以及中低收入国家自身免疫和过敏症减少的原因。
{"title":"Lifestyle score is associated with cellular immune profiles in healthy Tanzanian adults","authors":"Jeremia J. Pyuza , Marloes M.A.R. van Dorst , Koen Stam , Linda Wammes , Marion König , Vesla I. Kullaya , Yvonne Kruize , Wesley Huisman , Nikuntufya Andongolile , Anastazia Ngowi , Elichilia R. Shao , Alex Mremi , Pancras C.W. Hogendoorn , Sia E. Msuya , Simon P. Jochems , Wouter A.A. de Steenhuijsen Piters , Maria Yazdanbakhsh","doi":"10.1016/j.bbih.2024.100863","DOIUrl":"10.1016/j.bbih.2024.100863","url":null,"abstract":"<div><div>Immune system and vaccine responses vary across geographical locations worldwide, not only between high and low-middle income countries (LMICs), but also between rural and urban populations within the same country. Lifestyle factors such as housing conditions, exposure to microorganisms and parasites and diet are associated with rural-and urban-living. However, the relationships between these lifestyle factors and immune profiles have not been mapped in detail. Here, we profiled the immune system of 100 healthy Tanzanians living across four rural/urban areas using mass cytometry. We developed a lifestyle score based on an individual's household assets, housing condition and recent dietary history and studied the association with cellular immune profiles. Seventeen out of 80 immune cell clusters were associated with living location or lifestyle score, with eight identifiable only using lifestyle score. Individuals with low lifestyle score, most of whom live in rural settings, showed higher frequencies of NK cells, plasmablasts, atypical memory B cells, T helper 2 cells, regulatory T cells and activated CD4<sup>+</sup> T effector memory cells expressing CD38, HLA-DR and CTLA-4. In contrast, those with high lifestyle score, most of whom live in urban areas, showed a less activated state of the immune system illustrated by higher frequencies of naïve CD8<sup>+</sup> T cells. Using an elastic net machine learning model, we identified cellular immune signatures most associated with lifestyle score. Assuming a link between these immune profiles and vaccine responses, these signatures may inform us on the cellular mechanisms underlying poor responses to vaccines, but also reduced autoimmunity and allergies in low- and middle-income countries.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"41 ","pages":"Article 100863"},"PeriodicalIF":3.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.bbih.2024.100871
C. Wessa , J. Janssens , V. Coppens , K. El Abdellati , E. Vergaelen , S. van den Ameele , C. Baeken , D. Zeeuws , Y. Milaneschi , F. Lamers , B. Penninx , S. Claes , M. Morrens , L. De Picker
<div><h3>Introduction</h3><p>Different lines of evidence confirm the involvement of the immune system in the pathophysiology of major depressive disorder. Up to 30% of depressed patients present with an immune-mediated subtype, characterized by peripheral inflammation (high-sensitive C-reactive protein (hsCRP) ≥ 3 mg/l) and an atypical symptom profile with fatigue, anhedonia, increased appetite, and hypersomnia. This immune-mediated subtype of MDD is associated with poorer response to first-line antidepressant treatment. Consequently, strategies for immune-targeted augmentation should be prioritised towards patients with this subtype. Meta-analyses have shown modest but heterogeneous treatment effects with immune-targeted augmentation in unstratified MDD cohorts, with celecoxib and minocycline as most promising first-line treatment options. However, no study has prospectively evaluated the effectiveness of <em>a priori</em> stratification by baseline inflammation levels for add-on celecoxib or minocycline in MDD.</p></div><div><h3>Methods</h3><p>The INSTA-MD trial is a multicentre, 12-week, randomised, double-blind, placebo-controlled, parallel-group stratified clinical trial of adjunctive minocycline or celecoxib to treatment-as-usual for patients with MDD. Two hundred forty adult patients with Major Depressive Disorder who failed to remit with one or two trials of antidepressant treatment will be enrolled and allocated to high-hsCRP (hsCRP ≥3 mg/L) or low-hsCRP (hsCRP <3 mg/L) strata, where disproportional stratified sampling will ensure equally sized strata. Participants in each hsCRP stratum will be randomised to augment their ongoing antidepressant treatment with either adjunctive minocycline, celecoxib or placebo for a duration of 12 weeks, resulting in six treatment arms of each 40 participants. The primary objective is to evaluate the efficacy of immune-targeted augmentation with minocycline or celecoxib versus placebo, and the use of baseline hsCRP stratification to predict treatment response. Additionally, we will perform a head-to-head analysis between the two active compounds. The primary outcome measure is change in the Hamilton Depression Rating Scale (HDRS-17) total score. Secondary outcome measures will be response and remission rates, and change in inflammation-specific symptoms, adverse events and therapy acceptability (adherence). Further exploratory analyses will be performed with an array of peripheral inflammatory biomarkers, metabolic outcomes and physiological data.</p></div><div><h3>Expected impact</h3><p>The aim of INSTA-MD is to advance the use of immune-targeted precision psychiatry, by supporting the implementation of targeted hsCRP screening and treatment of immune-mediated MDD as a cost-effective intervention in primary care settings. Based on previous studies, we expect immune-targeted augmentation with minocycline or celecoxib to yield a superior remission rate of 15–30% compared to treatment as usual for immun
{"title":"Efficacy of inflammation-based stratification for add-on celecoxib or minocycline in major depressive disorder: Protocol of the INSTA-MD double-blind placebo-controlled randomised clinical trial","authors":"C. Wessa , J. Janssens , V. Coppens , K. El Abdellati , E. Vergaelen , S. van den Ameele , C. Baeken , D. Zeeuws , Y. Milaneschi , F. Lamers , B. Penninx , S. Claes , M. Morrens , L. De Picker","doi":"10.1016/j.bbih.2024.100871","DOIUrl":"10.1016/j.bbih.2024.100871","url":null,"abstract":"<div><h3>Introduction</h3><p>Different lines of evidence confirm the involvement of the immune system in the pathophysiology of major depressive disorder. Up to 30% of depressed patients present with an immune-mediated subtype, characterized by peripheral inflammation (high-sensitive C-reactive protein (hsCRP) ≥ 3 mg/l) and an atypical symptom profile with fatigue, anhedonia, increased appetite, and hypersomnia. This immune-mediated subtype of MDD is associated with poorer response to first-line antidepressant treatment. Consequently, strategies for immune-targeted augmentation should be prioritised towards patients with this subtype. Meta-analyses have shown modest but heterogeneous treatment effects with immune-targeted augmentation in unstratified MDD cohorts, with celecoxib and minocycline as most promising first-line treatment options. However, no study has prospectively evaluated the effectiveness of <em>a priori</em> stratification by baseline inflammation levels for add-on celecoxib or minocycline in MDD.</p></div><div><h3>Methods</h3><p>The INSTA-MD trial is a multicentre, 12-week, randomised, double-blind, placebo-controlled, parallel-group stratified clinical trial of adjunctive minocycline or celecoxib to treatment-as-usual for patients with MDD. Two hundred forty adult patients with Major Depressive Disorder who failed to remit with one or two trials of antidepressant treatment will be enrolled and allocated to high-hsCRP (hsCRP ≥3 mg/L) or low-hsCRP (hsCRP <3 mg/L) strata, where disproportional stratified sampling will ensure equally sized strata. Participants in each hsCRP stratum will be randomised to augment their ongoing antidepressant treatment with either adjunctive minocycline, celecoxib or placebo for a duration of 12 weeks, resulting in six treatment arms of each 40 participants. The primary objective is to evaluate the efficacy of immune-targeted augmentation with minocycline or celecoxib versus placebo, and the use of baseline hsCRP stratification to predict treatment response. Additionally, we will perform a head-to-head analysis between the two active compounds. The primary outcome measure is change in the Hamilton Depression Rating Scale (HDRS-17) total score. Secondary outcome measures will be response and remission rates, and change in inflammation-specific symptoms, adverse events and therapy acceptability (adherence). Further exploratory analyses will be performed with an array of peripheral inflammatory biomarkers, metabolic outcomes and physiological data.</p></div><div><h3>Expected impact</h3><p>The aim of INSTA-MD is to advance the use of immune-targeted precision psychiatry, by supporting the implementation of targeted hsCRP screening and treatment of immune-mediated MDD as a cost-effective intervention in primary care settings. Based on previous studies, we expect immune-targeted augmentation with minocycline or celecoxib to yield a superior remission rate of 15–30% compared to treatment as usual for immun","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"41 ","pages":"Article 100871"},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666354624001492/pdfft?md5=79510d8c32ceeea743bd91242d589a5c&pid=1-s2.0-S2666354624001492-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.bbih.2024.100870
Gabriel A. Frietze , Margie E. Padilla , Amanda M. Loya , Alyssa A. Martinez , Amir G. Hernandez , José O. Rivera
{"title":"Exploring predictors of COVID-19 precautionary behaviors during the initial rollout of COVID-19 vaccines in a predominately Hispanic sample","authors":"Gabriel A. Frietze , Margie E. Padilla , Amanda M. Loya , Alyssa A. Martinez , Amir G. Hernandez , José O. Rivera","doi":"10.1016/j.bbih.2024.100870","DOIUrl":"10.1016/j.bbih.2024.100870","url":null,"abstract":"","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"41 ","pages":"Article 100870"},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666354624001480/pdfft?md5=c1d8999c2453745ac8dab9e0e9927892&pid=1-s2.0-S2666354624001480-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142316097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.bbih.2024.100868
Riddhi A Laijawala
Recurrent pregnancy loss (RPL) is an obstetric condition estimated to affect 2–4% of childbearing individuals globally. Due to its varied nature, medical societies globally differ in their diagnostic criteria. Its aetiologies are numerous, ranging from anatomic abnormalities to endocrine and immunological factors. Autoimmune factors can attribute to approximately 20% of cases and include dysregulation of immune cells, cytokine production and antiphospholipid syndrome. Treatment pathways vary by aetiology; however, many cases remain unexplained, adding an additional level of complexity to this condition. Due to its recurrent nature, this type of pregnancy loss has profound impacts on mental health during subsequent pregnancies. While some aspects of RPL have been widely investigated, there continues to be a gap in research, such as its impacts on non-birthing parents and specific sociodemographic groups.
{"title":"Recurrent Pregnancy Loss: Immunological aetiologies and associations with mental health","authors":"Riddhi A Laijawala","doi":"10.1016/j.bbih.2024.100868","DOIUrl":"10.1016/j.bbih.2024.100868","url":null,"abstract":"<div><div>Recurrent pregnancy loss (RPL) is an obstetric condition estimated to affect 2–4% of childbearing individuals globally. Due to its varied nature, medical societies globally differ in their diagnostic criteria. Its aetiologies are numerous, ranging from anatomic abnormalities to endocrine and immunological factors. Autoimmune factors can attribute to approximately 20% of cases and include dysregulation of immune cells, cytokine production and antiphospholipid syndrome. Treatment pathways vary by aetiology; however, many cases remain unexplained, adding an additional level of complexity to this condition. Due to its recurrent nature, this type of pregnancy loss has profound impacts on mental health during subsequent pregnancies. While some aspects of RPL have been widely investigated, there continues to be a gap in research, such as its impacts on non-birthing parents and specific sociodemographic groups.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"41 ","pages":"Article 100868"},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142319397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.bbih.2024.100865
Harrison D. Collier-Bain , Annabelle Emery , Frankie F. Brown , Adam J. Causer , Rebecca Oliver , Rachel Eddy , Shoji Leach , John Graby , Daniel Augustine , Sally Moore , Josephine Crowe , James Murray , James E. Turner , John P. Campbell
Multiple myeloma is a haematological cancer characterised by the accumulation of clonal plasma cells in the bone marrow and is commonly treated with daratumumab, an anti-CD38 monoclonal antibody immunotherapy. Daratumumab often fails to induce stringent complete responses, due in part to resistance to antibody-dependent cellular cytotoxicity (ADCC) exerted by natural killer (NK)-cells and monocytes. Exercise bouts undertaken by healthy people induce lymphocytosis in blood, including to NK-cells and B-cells, but the effects of exercise are unknown in myeloma patients. In addition, whether exercise mobilises plasma cells has not been adequately investigated, and as such the potential impact of exercise on daratumumab treatment is unclear. In this exploratory pilot study, n = 16 smouldering multiple myeloma participants enrolled and n = 9 completed the study which comprised a bout of cycling 15% above anaerobic threshold for ∼30-min, with blood samples collected pre-, immediately post-, and 30-min post-exercise. Peripheral blood mononuclear cells were isolated from blood samples and incubated with the RPMI-8226 plasmacytoma cell line, with or without the presence of daratumumab to determine specific lysis using a calcein-release assay. Daratumumab-mediated cell lysis increased from 18.8% to 23.2% pre- to post-exercise, respectively (p < 0.001), owing to an increased frequency of CD3−CD56+CD16+ NK-cells (+348%), HLA-DR+CD14dimCD16+ monocytes (+125%), and HLA-DR+CD14+CD32+ monocytes (+41%) in blood (p < 0.01). However, overall, total plasma cells (CD38+CD138+) nor clonal plasma cells (CD38brightCD138+CD45−/dimCD19− with light-chain restriction) increased in blood (p > 0.05). Notably, we observed a 305% increase in NK-cells expressing CD38, the daratumumab target antigen, which might render NK-cells more susceptible to daratumumab-mediated fratricide – whereby NK-cells initiate ADCC against daratumumab-bound NK-cells. In conclusion, exercise modestly improved the efficacy of daratumumab-mediated ADCC in vitro. However, plasma cells were largely unchanged, and NK-cells expressing CD38 – the daratumumab target antigen – increased in blood. Future research should consider the optimal timings of exercise during daratumumab treatment in myeloma to avert exacerbation of daratumumab-mediated NK-cell lysis.
{"title":"Characterising how a single bout of exercise in people with myeloma affects clonal plasma cell and immune effector cell frequency in blood, and daratumumab efficacy in vitro","authors":"Harrison D. Collier-Bain , Annabelle Emery , Frankie F. Brown , Adam J. Causer , Rebecca Oliver , Rachel Eddy , Shoji Leach , John Graby , Daniel Augustine , Sally Moore , Josephine Crowe , James Murray , James E. Turner , John P. Campbell","doi":"10.1016/j.bbih.2024.100865","DOIUrl":"10.1016/j.bbih.2024.100865","url":null,"abstract":"<div><div>Multiple myeloma is a haematological cancer characterised by the accumulation of clonal plasma cells in the bone marrow and is commonly treated with daratumumab, an anti-CD38 monoclonal antibody immunotherapy. Daratumumab often fails to induce stringent complete responses, due in part to resistance to antibody-dependent cellular cytotoxicity (ADCC) exerted by natural killer (NK)-cells and monocytes. Exercise bouts undertaken by healthy people induce lymphocytosis in blood, including to NK-cells and B-cells, but the effects of exercise are unknown in myeloma patients. In addition, whether exercise mobilises plasma cells has not been adequately investigated, and as such the potential impact of exercise on daratumumab treatment is unclear. In this exploratory pilot study, <em>n</em> = 16 smouldering multiple myeloma participants enrolled and <em>n</em> = 9 completed the study which comprised a bout of cycling 15% above anaerobic threshold for ∼30-min, with blood samples collected pre-, immediately post-, and 30-min post-exercise. Peripheral blood mononuclear cells were isolated from blood samples and incubated with the RPMI-8226 plasmacytoma cell line, with or without the presence of daratumumab to determine specific lysis using a calcein-release assay. Daratumumab-mediated cell lysis increased from 18.8% to 23.2% pre- to post-exercise, respectively (<em>p</em> < 0.001), owing to an increased frequency of CD3<sup>−</sup>CD56<sup>+</sup>CD16<sup>+</sup> NK-cells (+348%), HLA-DR<sup>+</sup>CD14<sup>dim</sup>CD16<sup>+</sup> monocytes (+125%), and HLA-DR<sup>+</sup>CD14<sup>+</sup>CD32<sup>+</sup> monocytes (+41%) in blood (<em>p</em> < 0.01). However, overall, total plasma cells (CD38<sup>+</sup>CD138<sup>+</sup>) nor clonal plasma cells (CD38<sup>bright</sup>CD138<sup>+</sup>CD45<sup>−/dim</sup>CD19<sup>−</sup> with light-chain restriction) increased in blood (<em>p</em> > 0.05). Notably, we observed a 305% increase in NK-cells expressing CD38, the daratumumab target antigen, which might render NK-cells more susceptible to daratumumab-mediated fratricide – whereby NK-cells initiate ADCC against daratumumab-bound NK-cells. In conclusion, exercise modestly improved the efficacy of daratumumab-mediated ADCC <em>in vitro</em>. However, plasma cells were largely unchanged, and NK-cells expressing CD38 – the daratumumab target antigen – increased in blood. Future research should consider the optimal timings of exercise during daratumumab treatment in myeloma to avert exacerbation of daratumumab-mediated NK-cell lysis.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100865"},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-19DOI: 10.1016/j.bbih.2024.100855
Rafael R. Ferreira , Ronaldo B. Martins , Isabela Pires , Bruno L. Marques , Karla C.M. Costa , Pedro H.C. Lirio , Davi S. Scomparin , Franciele F. Scarante , Sabrina S. Batah , Jaime E.C. Hallak , Jose A. Crippa , Livia C.M. Rodrigues , Rita C. Tostes , Alexandre T. Fabro , Eurico Arruda , Alline C. Campos
Even though respiratory dysfunctions are the primary symptom associated with SARS-CoV-2 infection, cerebrovascular events, and neurological symptoms are described in many patients. However, the connection between the neuroimmune profile and the lung's inflammatory condition during COVID-19 and its association with the neurological symptoms reported by COVID-19 patients still needs further exploration. The present study characterizes the SARS-CoV-2 infectivity profile in postmortem nervous and lung tissue samples of patients who died due to severe COVID-19, and the pro-inflammatory factors present in both nervous and lung tissue samples, via a proteomic profiling array. Additionally, Brain-Derived Neurotrophic Factor (BDNF) levels and intracellular pathways related to neuroplasticity/neuroprotection were assessed in the samples. Out of the 16 samples analyzed, all samples but 1 were positive for the viral genome (genes E or N2, but only 3.9% presented E and N2) in the olfactory brain pathway. The E or N2 gene were also detected in all lung samples, with 43.7% of the samples being positive for the E and N2 genes. In the E/N2 positive brain samples, the Spike protein of SARS-CoV-2 co-localized with TUJ-1+ (neuron-specific class III beta-tubulin) and GFAP+ (glial fibrillary acidic protein) astrocytes. IL-6, but not IL-10, expression was markedly higher in most nervous tissue samples compared to the lung specimens. While intracellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF), and plasminogen activator inhibitor 1 (PAI-1) were increased in lung samples from SARS-Cov-2 patients, only MIF and IL-18 were detected in nervous tissue samples. Correlation analysis suggested that high levels of IL-6 are followed by increased levels of IL-10 in the brain, but not in lung samples. Our analysis also demonstrated that the presence of comorbidities, such as cardiovascular disease, hypertension, and hypothyroidism, is associated with neuroinflammation, while chronic kidney conditions predict the presence of neurological symptoms, which correlate with lower levels of BDNF in the brain samples. Our results corroborate the hypothesis that a pro-inflammatory state might further impair neural homeostasis and induce brain abnormalities found in COVID-19 patients.
{"title":"Cardiovascular and kidney diseases are positively associated with neuroinflammation and reduced brain-derived neurotrophic factor in patients with severe COVID-19","authors":"Rafael R. Ferreira , Ronaldo B. Martins , Isabela Pires , Bruno L. Marques , Karla C.M. Costa , Pedro H.C. Lirio , Davi S. Scomparin , Franciele F. Scarante , Sabrina S. Batah , Jaime E.C. Hallak , Jose A. Crippa , Livia C.M. Rodrigues , Rita C. Tostes , Alexandre T. Fabro , Eurico Arruda , Alline C. Campos","doi":"10.1016/j.bbih.2024.100855","DOIUrl":"10.1016/j.bbih.2024.100855","url":null,"abstract":"<div><div>Even though respiratory dysfunctions are the primary symptom associated with SARS-CoV-2 infection, cerebrovascular events, and neurological symptoms are described in many patients. However, the connection between the neuroimmune profile and the lung's inflammatory condition during COVID-19 and its association with the neurological symptoms reported by COVID-19 patients still needs further exploration. The present study characterizes the SARS-CoV-2 infectivity profile in <em>postmortem</em> nervous and lung tissue samples of patients who died due to severe COVID-19, and the pro-inflammatory factors present in both nervous and lung tissue samples, via a proteomic profiling array. Additionally, Brain-Derived Neurotrophic Factor (BDNF) levels and intracellular pathways related to neuroplasticity/neuroprotection were assessed in the samples. Out of the 16 samples analyzed, all samples but 1 were positive for the viral genome (genes E or N2, but only 3.9% presented E and N2) in the olfactory brain pathway. The E or N2 gene were also detected in all lung samples, with 43.7% of the samples being positive for the E and N2 genes. In the E/N2 positive brain samples, the Spike protein of SARS-CoV-2 co-localized with TUJ-1+ (neuron-specific class III beta-tubulin) and GFAP+ (glial fibrillary acidic protein) astrocytes. IL-6, but not IL-10, expression was markedly higher in most nervous tissue samples compared to the lung specimens. While intracellular adhesion molecule-1 (ICAM-1), interleukin-8 (IL-8), macrophage migration inhibitory factor (MIF), and plasminogen activator inhibitor 1 (PAI-1) were increased in lung samples from SARS-Cov-2 patients, only MIF and IL-18 were detected in nervous tissue samples. Correlation analysis suggested that high levels of IL-6 are followed by increased levels of IL-10 in the brain, but not in lung samples. Our analysis also demonstrated that the presence of comorbidities, such as cardiovascular disease, hypertension, and hypothyroidism, is associated with neuroinflammation, while chronic kidney conditions predict the presence of neurological symptoms, which correlate with lower levels of BDNF in the brain samples. Our results corroborate the hypothesis that a pro-inflammatory state might further impair neural homeostasis and induce brain abnormalities found in COVID-19 patients.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"41 ","pages":"Article 100855"},"PeriodicalIF":3.7,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-17DOI: 10.1016/j.bbih.2024.100859
Steven Brem
Immuno-oncology, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer care with dramatic, long-term responses and increased survival, including patients with metastatic cancer to the brain. Glioblastomas, and other primary brain tumors, are refractory to ICIs as monotherapy or in combination with standard therapy. The tumor microenvironment (TME) poses multiple biological hurdles: blood-brain barrier, immune suppression, heterogeneity, and tumor infiltration. Genomic analysis of the senescence-associated secretory phenotype (SASP) and preclinical models of glioma suggest that an exciting approach would entail reprogramming of the glioma microenvironment, attenuating the pro-inflammatory, pro-tumorigenic cytokines of the SASP, especially interleukin-6 (IL-6). A testable hypothesis now proposed is to modulate the immune system by harnessing the body's ‘inflammatory reflex’ to reduce cytokines. Vagus nerve stimulation can activate T cell immunity by the cholinergic, α7nicotinic acetylcholine receptor agonist (α7nAchR), and suppress IL-6 systemically, as well as other pro-inflammatory cytokines of the SASP, interleukin -1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). The hypothesis predicts that electrical activation of the vagus nerve, with cytokine reduction, in combination with ICIs, would convert an immune resistant (“cold”) tumor to an immune responsive (“hot”) tumor, and halt glioma progression. The hypothesis also envisions cancer as an immune “dysautonomia” whereby a therapeutic intervention, vagus nerve stimulation (VNS), resets the systemic and local cytokine levels. A prospective, randomized, phase II clinical trial, to confirm the hypothesis, is a logical, exigent, next step. Cytokine reduction by VNS could also be useful for other forms of human cancer, e.g., breast, colorectal, head and neck, lung, melanoma, ovarian, pancreatic, and prostate cancer, as the emerging field of “cancer neuroscience” shows a role for neural regulation of multiple tumor types. Because IL-6, and companion pro-inflammatory cytokines, participate in the initiation, progression, spread and recurrence of cancer, minimally invasive VNS could be employed to suppress glioma or cancer progression, while also mitigating depression and/or seizures, thereby enhancing quality of life. The current hypothesis reimagines glioma pathophysiology as a dysautonomia with the therapeutic objective to reset the autonomic nervous system and form an immune responsive state to halt tumor progression and prevent recurrence. VNS, as a novel method to control cancer, can be administered with ICIs, standard therapy, or in clinical trials, combined with emerging immunotherapy: dendritic cell, mRNA, or chimeric antigen receptor (CAR) T cell vaccines.
{"title":"Vagus nerve stimulation: Novel concept for the treatment of glioblastoma and solid cancers by cytokine (interleukin-6) reduction, attenuating the SASP, enhancing tumor immunity","authors":"Steven Brem","doi":"10.1016/j.bbih.2024.100859","DOIUrl":"10.1016/j.bbih.2024.100859","url":null,"abstract":"<div><div>Immuno-oncology, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer care with dramatic, long-term responses and increased survival, including patients with metastatic cancer to the brain. Glioblastomas, and other primary brain tumors, are refractory to ICIs as monotherapy or in combination with standard therapy. The tumor microenvironment (TME) poses multiple biological hurdles: blood-brain barrier, immune suppression, heterogeneity, and tumor infiltration. Genomic analysis of the senescence-associated secretory phenotype (SASP) and preclinical models of glioma suggest that an exciting approach would entail reprogramming of the glioma microenvironment, attenuating the pro-inflammatory, pro-tumorigenic cytokines of the SASP, especially interleukin-6 (IL-6). A testable hypothesis now proposed is to modulate the immune system by harnessing the body's ‘inflammatory reflex’ to reduce cytokines. Vagus nerve stimulation can activate T cell immunity by the cholinergic, α7nicotinic acetylcholine receptor agonist (α7nAchR), and suppress IL-6 systemically, as well as other pro-inflammatory cytokines of the SASP, interleukin -1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). The hypothesis predicts that electrical activation of the vagus nerve, with cytokine reduction, in combination with ICIs, would convert an immune resistant (“cold”) tumor to an immune responsive (“hot”) tumor, and halt glioma progression. The hypothesis also envisions cancer as an immune “dysautonomia” whereby a therapeutic intervention, vagus nerve stimulation (VNS), resets the systemic and local cytokine levels. A prospective, randomized, phase II clinical trial, to confirm the hypothesis, is a logical, exigent, next step. Cytokine reduction by VNS could also be useful for other forms of human cancer, e.g., breast, colorectal, head and neck, lung, melanoma, ovarian, pancreatic, and prostate cancer, as the emerging field of “cancer neuroscience” shows a role for neural regulation of multiple tumor types. Because IL-6, and companion pro-inflammatory cytokines, participate in the initiation, progression, spread and recurrence of cancer, minimally invasive VNS could be employed to suppress glioma or cancer progression, while also mitigating depression and/or seizures, thereby enhancing quality of life. The current hypothesis reimagines glioma pathophysiology as a dysautonomia with the therapeutic objective to reset the autonomic nervous system and form an immune responsive state to halt tumor progression and prevent recurrence. VNS, as a novel method to control cancer, can be administered with ICIs, standard therapy, or in clinical trials, combined with emerging immunotherapy: dendritic cell, mRNA, or chimeric antigen receptor (CAR) T cell vaccines.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"42 ","pages":"Article 100859"},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142528567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1016/j.bbih.2024.100869
Elena M. Faioni , Luca Imeri , Alice Bonomi , Arianna Galotta , Vanessa Guerra , Luca Pase , Susanna Bianchi , Maria L. Biondi
Since previous studies, mostly performed in healthy adults, show that sleep restriction around time of vaccination impairs antibody response and shift work affects sleep, aim of the study was to test the hypothesis that the antibody response to vaccination is impaired in shift workers, when compared to non-shift workers.
Employees (n = 445; mean age 44 ± 11 years; 35 % men) of the Centro Cardiologico Monzino, IRCCS (Milan, Italy) were vaccinated against SARS-CoV2 in February 2021 with an mRNA-based vaccine. Antibody titers were assayed 1 and 7 months later. Differences between groups were assessed using ANOVA, after log-transformation of variables with right-skewed distribution.
We report that the antibody titer was significantly higher in shift workers (33 % of employees) compared to non-shift workers at first assay [median (IQR): 2495 (1700; 4665) vs 2060 (1619; 2970) BAU/mL, p = 0.0123], as well as at the second one, and that this difference was abolished after adjustment for previous development of symptomatic COVID-19. Results were not affected by age or sex at birth.
These results show that shift workers were able to mount an unimpaired antibody response to vaccination. Since vaccinations were performed during the pandemic urgency, our retrospective study has several limitations, nevertheless it underlines the need for large prospective, controlled studies on the effects of acute and chronic sleep restriction on response to vaccination in the general population and on the impact of shift work on immune response.
{"title":"Humoral response to anti SARS-CoV2 vaccination at one and seven months is not different in shift workers and non-shift workers","authors":"Elena M. Faioni , Luca Imeri , Alice Bonomi , Arianna Galotta , Vanessa Guerra , Luca Pase , Susanna Bianchi , Maria L. Biondi","doi":"10.1016/j.bbih.2024.100869","DOIUrl":"10.1016/j.bbih.2024.100869","url":null,"abstract":"<div><p>Since previous studies, mostly performed in healthy adults, show that sleep restriction around time of vaccination impairs antibody response and shift work affects sleep, aim of the study was to test the hypothesis that the antibody response to vaccination is impaired in shift workers, when compared to non-shift workers.</p><p>Employees (n = 445; mean age 44 ± 11 years; 35 % men) of the Centro Cardiologico Monzino, IRCCS (Milan, Italy) were vaccinated against SARS-CoV2 in February 2021 with an mRNA-based vaccine. Antibody titers were assayed 1 and 7 months later. Differences between groups were assessed using ANOVA, after log-transformation of variables with right-skewed distribution.</p><p>We report that the antibody titer was significantly higher in shift workers (33 % of employees) compared to non-shift workers at first assay [median (IQR): 2495 (1700; 4665) <em>vs</em> 2060 (1619; 2970) BAU/mL, p = 0.0123], as well as at the second one, and that this difference was abolished after adjustment for previous development of symptomatic COVID-19. Results were not affected by age or sex at birth.</p><p>These results show that shift workers were able to mount an unimpaired antibody response to vaccination. Since vaccinations were performed during the pandemic urgency, our retrospective study has several limitations, nevertheless it underlines the need for large prospective, controlled studies on the effects of acute and chronic sleep restriction on response to vaccination in the general population and on the impact of shift work on immune response.</p></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"41 ","pages":"Article 100869"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666354624001479/pdfft?md5=91bdec778d8029b6b25f4fdb85a40897&pid=1-s2.0-S2666354624001479-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1016/j.bbih.2024.100864
Per Thunberg , David Fresnais , Paul Hamilton , Susanne Bejerot , Mats B. Humble
Neuroinflammation has been implicated in the pathophysiology of schizophrenia and obsessive-compulsive disorder (OCD) and deviations in brain structure and connectivity are seen in these disorders. Here, we explore the effects of a potent immunomodulatory treatment on neuroimaging. In a pilot study of rituximab treatment in schizophrenia and OCD, a subgroup (n = 13) underwent structural and functional magnetic resonance imaging before and 5 months after treatment, to study longitudinal changes in resting-state functional connectivity (rsFC) and voxel-based morphometry (VBM).
A hypothesis-free exploratory whole-brain analysis was performed twice to assess changes in rsFC, using anterior cingulate cortex, anterior insula, posterior insula and nucleus accumbens as seed regions. There were significant interactions (diagnosis x time) in connectivity between right posterior insula and two clusters encompassing basal ganglia and anterior frontal pole, and between left anterior insula and a cluster in basal ganglia, where connectivity decreased in OCD and increased in schizophrenia. The increase of connectivity after rituximab, between left anterior insula and parts of cerebellum and lingual gyrus and between left posterior insula and parts of cerebellum, correlated with improved global psychosocial functioning according to the Personal and Social Performance Scale, especially in schizophrenia. VBM analysis identified two clusters with increased grey matter volumes (GMV) after rituximab, one in right insula overlapping one of the seed regions with significant rsFC changes. This pilot study implies that rituximab may influence both brain structure and connectivity and that GMV changes and rsFC changes are regionally associated.
神经炎症与精神分裂症和强迫症（OCD）的病理生理学有关，这些疾病的大脑结构和连通性都存在偏差。在此，我们探讨了强效免疫调节治疗对神经影像学的影响。在一项利妥昔单抗治疗精神分裂症和强迫症的试验性研究中，一个亚组（n = 13）在治疗前和治疗后5个月接受了结构和功能磁共振成像检查，以研究静息态功能连通性（rsFC）和基于体素的形态测量（VBM）的纵向变化。以前扣带回皮层、前岛叶、后岛叶和伏隔核为种子区域，进行了两次无假设探索性全脑分析，以评估rsFC的变化。右侧后脑岛与包括基底节和前额极在内的两个簇之间，以及左侧前脑岛与基底节中的一个簇之间的连通性存在明显的交互作用（诊断×时间），其中强迫症患者的连通性下降，而精神分裂症患者的连通性上升。利妥昔单抗治疗后，左前岛叶与小脑部分区域和舌回之间以及左后岛叶与小脑部分区域之间的连接性增加，与个人和社会表现量表（Personal and Social Performance Scale）显示的全球社会心理功能改善相关，尤其是在精神分裂症患者中。VBM分析发现了利妥昔单抗治疗后灰质体积（GMV）增加的两个集群，其中一个位于右侧岛叶，与rsFC发生显著变化的一个种子区域重叠。这项试验性研究表明，利妥昔单抗可能同时影响大脑结构和连通性，而且GMV变化和rsFC变化在区域上是相关的。
{"title":"Immunomodulatory treatment may change functional and structural brain imaging in severe mental disorders","authors":"Per Thunberg , David Fresnais , Paul Hamilton , Susanne Bejerot , Mats B. Humble","doi":"10.1016/j.bbih.2024.100864","DOIUrl":"10.1016/j.bbih.2024.100864","url":null,"abstract":"<div><p>Neuroinflammation has been implicated in the pathophysiology of schizophrenia and obsessive-compulsive disorder (OCD) and deviations in brain structure and connectivity are seen in these disorders. Here, we explore the effects of a potent immunomodulatory treatment on neuroimaging. In a pilot study of rituximab treatment in schizophrenia and OCD, a subgroup (n = 13) underwent structural and functional magnetic resonance imaging before and 5 months after treatment, to study longitudinal changes in resting-state functional connectivity (rsFC) and voxel-based morphometry (VBM).</p><p>A hypothesis-free exploratory whole-brain analysis was performed twice to assess changes in rsFC, using anterior cingulate cortex, anterior insula, posterior insula and nucleus accumbens as seed regions. There were significant interactions (diagnosis x time) in connectivity between right posterior insula and two clusters encompassing basal ganglia and anterior frontal pole, and between left anterior insula and a cluster in basal ganglia, where connectivity decreased in OCD and increased in schizophrenia. The increase of connectivity after rituximab, between left anterior insula and parts of cerebellum and lingual gyrus and between left posterior insula and parts of cerebellum, correlated with improved global psychosocial functioning according to the Personal and Social Performance Scale, especially in schizophrenia. VBM analysis identified two clusters with increased grey matter volumes (GMV) after rituximab, one in right insula overlapping one of the seed regions with significant rsFC changes. This pilot study implies that rituximab may influence both brain structure and connectivity and that GMV changes and rsFC changes are regionally associated.</p></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"41 ","pages":"Article 100864"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266635462400142X/pdfft?md5=4fe0f2e05856a3bbfe327dace9137850&pid=1-s2.0-S266635462400142X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16DOI: 10.1016/j.bbih.2024.100862
Laura Morrison , Adam H. Dyer , Helena Dolphin , Isabella Batten , Conor Reddy , Matthew Widdowson , Conor P. Woods , James Gibney , Nollaig M. Bourke , Sean P. Kennelly
Midlife cardiovascular risk factors such as Type 2 Diabetes (T2DM) and obesity are associated with the later development of cognitive impairment and dementia. Systemic inflammation is postulated as a crucial mechanism, yet there are few studies examining this at the earliest stages prior to overt cognitive impairment. To assess this, we recruited a cohort of middle-aged cognitively-unimpaired individuals with and without uncomplicated T2DM. Comprehensive neuropsychological assessment was performed at baseline and at 4-year follow-up. Ten serum chemokines and cytokines (Eotaxin, MCP-1, MIP-1β, CXCL10, IL-6, IL-10, IL12p70, IL-17A, IFN-γ and TNF-α) were measured at both baseline and follow-up using high-sensitivity assays. Overall, 136 participants were recruited including 90 with uncomplicated midlife T2DM (age 52.6 ± 8.3; 47% female) and 46 without (age 52.9 ± 8.03; 61% female). Cognitive trajectories were stable over time and did not differ with T2DM. Yet on cross-sectional analyses at both baseline and follow-up, greater circulating IL-17A was consistently associated with poorer performance on tests of executive function/attention (β: 0.21; −0.40, −0.02, p = 0.03 at baseline; β: 0.26; −0.46, −0.05, p = 0.02 at follow-up). Associations persisted on covariate adjustment and did not differ by T2DM status. In summary, we provide evidence that greater circulating IL-17A levels were associated with poorer executive function in midlife, independent of T2DM. Long-term follow-up of this and other cohorts will further elucidate the earliest stages in the relationship between systemic inflammation and cognitive decline to provide further mechanistic insights and potentially identify those at greatest risk for later cognitive decline.
{"title":"Circulating Interleukin-17A is associated with executive function in middle aged adults with and without type 2 diabetes","authors":"Laura Morrison , Adam H. Dyer , Helena Dolphin , Isabella Batten , Conor Reddy , Matthew Widdowson , Conor P. Woods , James Gibney , Nollaig M. Bourke , Sean P. Kennelly","doi":"10.1016/j.bbih.2024.100862","DOIUrl":"10.1016/j.bbih.2024.100862","url":null,"abstract":"<div><p>Midlife cardiovascular risk factors such as Type 2 Diabetes (T2DM) and obesity are associated with the later development of cognitive impairment and dementia. Systemic inflammation is postulated as a crucial mechanism, yet there are few studies examining this at the earliest stages prior to overt cognitive impairment. To assess this, we recruited a cohort of middle-aged cognitively-unimpaired individuals with and without uncomplicated T2DM. Comprehensive neuropsychological assessment was performed at baseline and at 4-year follow-up. Ten serum chemokines and cytokines (Eotaxin, MCP-1, MIP-1β, CXCL10, IL-6, IL-10, IL12p70, IL-17A, IFN-γ and TNF-α) were measured at both baseline and follow-up using high-sensitivity assays. Overall, 136 participants were recruited including 90 with uncomplicated midlife T2DM (age 52.6 ± 8.3; 47% female) and 46 without (age 52.9 ± 8.03; 61% female). Cognitive trajectories were stable over time and did not differ with T2DM. Yet on cross-sectional analyses at both baseline and follow-up, greater circulating IL-17A was consistently associated with poorer performance on tests of executive function/attention (β: 0.21; −0.40, −0.02, p = 0.03 at baseline; β: 0.26; −0.46, −0.05, p = 0.02 at follow-up). Associations persisted on covariate adjustment and did not differ by T2DM status. In summary, we provide evidence that greater circulating IL-17A levels were associated with poorer executive function in midlife, independent of T2DM. Long-term follow-up of this and other cohorts will further elucidate the earliest stages in the relationship between systemic inflammation and cognitive decline to provide further mechanistic insights and potentially identify those at greatest risk for later cognitive decline.</p></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"41 ","pages":"Article 100862"},"PeriodicalIF":3.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666354624001406/pdfft?md5=cd5bf33b4d7873276ca0aa7922125495&pid=1-s2.0-S2666354624001406-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270320","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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