Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Natalizumab Treatment Induces Proinflammatory CD4 T Cells Preferentially in the Integrin β7+ Compartment.","authors":"Mélanie Nguyen Ky, Adrien Duran, Iris Hasantari, Agnès Bru, Mathilde Deloire, Bruno Brochet, Aurélie Ruet, Nathalie Schmitt","doi":"10.1212/NXI.0000000000200166","DOIUrl":"10.1212/NXI.0000000000200166","url":null,"abstract":"<p><strong>Background and objectives: </strong>Natalizumab, a monoclonal humanized antibody targeting integrin α4, inhibits the transmigration of lymphocytes into the CNS by preventing the interaction of integrin α4β1 with V-CAM expressed on brain vascular endothelial cells. Although natalizumab treatment reduces the clinical relapse rate in patients with relapsing-remitting MS, its discontinuation after reactivation of the JC virus is associated with a rebound of the disease in 20% of patients. The mechanisms of this rebound are not elucidated, but natalizumab increases the frequencies of circulating CD4 T cells expressing proinflammatory cytokines as well as the proportion of circulating Th17/Th1 cells (Th1-like Th17 cells). Gut-derived memory CD4 T cells are a population of growing interest in the pathogenesis of MS, but whether and how their properties are affected by natalizumab is not known. Here, we studied the phenotype and cytokine expression profile of circulating gut-derived memory CD4 T cells in patients with relapsing-remitting MS under natalizumab.</p><p><strong>Methods: </strong>We identified gut-derived memory CD4 T cells by their expression of integrin β7 and compared their properties and those of integrin β7- memory CD4 T cells across healthy donors and patients with relapsing-remitting MS treated or not with natalizumab. We also compared the capacity of integrin β7- and integrin β7+ CD4 T-cell subsets to transmigrate in vitro across a model of blood-brain barrier.</p><p><strong>Results: </strong>The proportions of proinflammatory Th17/Th1 cells as well as of IL-17A+IFNγ+ and IL-17A+GM-CSF+ cells were higher in memory CD4 T cells expressing integrin β7 in patients receiving natalizumab compared with healthy donors and patients with relapsing-remitting MS not receiving natalizumab. By contrast, integrin β7 negative memory CD4 T cells only presented a modest increased in their proportion of Th17/Th1 cells under natalizumab. We further observed that integrin β7+ Th17/Th1 cells migrated as efficiently as integrin β7- Th17/Th1 across a monolayer of brain microvascular endothelial cells.</p><p><strong>Discussion: </strong>Our study shows that circulating integrin β7+ memory CD4 T cells of patients with relapsing-remitting MS under natalizumab are enriched in proinflammatory cells supporting the hypothesis that integrin β7+ memory CD4 T cells could play a pathogenic role in the disease rebound observed at natalizumab discontinuation.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"10 6","pages":""},"PeriodicalIF":8.8,"publicationDate":"2023-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/24/88/NXI-2023-000126.PMC10519437.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Siponimod Inhibits the Formation of Meningeal Ectopic Lymphoid Tissue in Experimental Autoimmune Encephalomyelitis","authors":"","doi":"10.1212/NXI.0000000000001174","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001174","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"9 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43357395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline Microglial Activation Correlates With Brain Amyloidosis and Longitudinal Cognitive Decline in Alzheimer Disease.","authors":"Qing Wang, Gengsheng Chen, Suzanne E Schindler, Jon Christensen, Nicole S McKay, Jingxia Liu, Sicheng Wang, Zhexian Sun, Jason Hassenstab, Yi Su, Shaney Flores, Russ Hornbeck, Lisa Cash, Carlos Cruchaga, Anne M Fagan, Zhude Tu, John C Morris, Mark A Mintun, Yong Wang, Tammie L S Benzinger","doi":"10.1212/NXI.0000000000001152","DOIUrl":"10.1212/NXI.0000000000001152","url":null,"abstract":"<p><strong>Background and objectives: </strong>This study aims to quantify microglial activation in individuals with Alzheimer disease (AD) using the 18-kDa translocator protein (TSPO) PET imaging in the hippocampus and precuneus, the 2 AD-vulnerable regions, and to evaluate the association of baseline neuroinflammation with amyloidosis, tau, and longitudinal cognitive decline.</p><p><strong>Methods: </strong>Twenty-four participants from the Knight Alzheimer Disease Research Center (Knight ADRC) were enrolled and classified into stable cognitively normal, progressor, and symptomatic AD groups based on clinical dementia rating (CDR) at 2 or more clinical assessments. The baseline TSPO radiotracer [11C]PK11195 was used to image microglial activation. Baseline CSF concentrations of Aβ42, Aβ42/Aβ40 ratio, tau phosphorylated at position 181 (p-tau181), and total tau (t-tau) were measured. Clinical and cognitive decline were examined with longitudinal CDR and cognitive composite scores (Global and Knight ADRC-Preclinical Alzheimer Cognitive Composite [Knight ADRC-PACC] Score).</p><p><strong>Results: </strong>Participants in the progressor and symptomatic AD groups had significantly elevated [11C]PK11195 standard uptake value ratios (SUVRs) in the hippocampus but not in the precuneus region. In the subcohort with CSF biomarkers (16 of the 24), significant negative correlations between CSF Aβ42 or Aβ42/Aβ40 and [11C]PK11195 SUVR were observed in the hippocampus and precuneus. No correlations were observed between [11C]PK11195 SUVR and CSF p-tau181 or t-tau at baseline in those regions. Higher baseline [11C]PK11195 SUVR averaged in the whole cortical regions predicted longitudinal decline on cognitive tests.</p><p><strong>Discussion: </strong>Microglial activation is increased in individuals with brain amyloidosis and predicts worsening cognition in AD.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that in patients with AD, higher baseline [11C]PK11195 SUVR averaged in the whole cortical regions was associated with longitudinal decline on cognitive tests.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"9 3","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ff/73/NEURIMMINFL2021039348.PMC8906187.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"61564314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurology Neuroimmunology & Neuroinflammation's Acknowledgment to Reviewers","authors":"","doi":"10.1212/NXI.0000000000001002","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001002","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"8 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44675032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL6 receptor358Ala variant and trans-signaling are disease modifiers in amyotrophic lateral sclerosis","authors":"L. Wilkins","doi":"10.1212/NXI.0000000000000650","DOIUrl":"https://doi.org/10.1212/NXI.0000000000000650","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"7 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1212/NXI.0000000000000650","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43730365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A case of idiopathic multicentric Castleman disease in an alemtuzumab-treated patient with MS","authors":"L. Wilkins","doi":"10.1212/NXI.0000000000000657","DOIUrl":"https://doi.org/10.1212/NXI.0000000000000657","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2019-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1212/NXI.0000000000000657","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49500158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholecalciferol in relapsing-remitting MS: A randomized clinical trial (CHOLINE)","authors":"L. Wilkins","doi":"10.1212/NXI.0000000000000648","DOIUrl":"https://doi.org/10.1212/NXI.0000000000000648","url":null,"abstract":"Articles appearing in the September 2019 issue Relationship between retinal inner nuclear layer, age, and disease activity in progressive MS Objective To investigate whether inner nuclear layer (INL) thickness as assessed with optical coherence tomography differs between patients with progressive MS (P-MS) according to age and disease activity. Methods In this retrospective longitudinal analysis, differences in terms of peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer + inner plexiform layer (GCIPL), INL andT1/T2 lesion volumes (T1LV/T2LV)were assessed between 84 patients with P-MS and 36 sexand age-matched healthy controls (HCs) and between patients stratified according to age (cut-off: 51 years) and evidence of clinical/MRI activity in the previous 12 months Results pRNFL and GCIPL thickness were significantly lower in patients with P-MS than in HCs (p = 0.003 and p < 0.0001, respectively). INL was significantly thicker in patients aged <51 years compared to the older ones and HCs (38.2 vs 36.5 and 36.7 μm; p = 0.038 and p = 0.04, respectively) and in those who presented MRI activity (new T2/gadolinium-enhancing lesions) in the previous 12 months compared to the ones who did not and HCs (39.5 vs 36.4 and 36.7 μm; p = 0.003 and p = 0.008, respectively). Recent MRI activity was significantly predicted by greater INL thickness (Nagelkerke R 0.36, p = 0.001). Conclusions INL thickness was higher in younger patients with P-MS with recent MRI activity, a criterion used in previous studies to identify a specific subset of patients with P-MS who best responded to diseasemodifying treatment. If this finding is confirmed, we suggest that INL thickness might be a useful tool in stratification of patients with P-MS for current and experimental treatment choice.","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2019-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1212/NXI.0000000000000648","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45718301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of circulating MOG-specific B cells in patients with MOG antibodies","authors":"L. Wilkins","doi":"10.1212/NXI.0000000000000647","DOIUrl":"https://doi.org/10.1212/NXI.0000000000000647","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2019-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1212/NXI.0000000000000647","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47128096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α4-integrin deficiency in B cells does not affect disease in a T-cell–mediated EAE disease model","authors":"L. Wilkins","doi":"10.1212/NXI.0000000000000585","DOIUrl":"https://doi.org/10.1212/NXI.0000000000000585","url":null,"abstract":"[This corrects the article on p. e563 in vol. 6, PMID: 31086806.].","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"6 1","pages":""},"PeriodicalIF":8.8,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1212/NXI.0000000000000585","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43109792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A surprise with MuSK antibodies","authors":"J. Dalmau","doi":"10.1212/NXI.0000000000000564","DOIUrl":"https://doi.org/10.1212/NXI.0000000000000564","url":null,"abstract":"This issue of Neurology® Neuroimmunology & Neuroinflammation (N2) contains several studies that reveal surprising or unexpected findings such as the mechanisms underlying muscle-specific kinase (MuSK) antibody pathogenicity, presence of inflammatory cells in normal muscle, and the isolated CNS manifestation of a systemic disease. Here is a brief overview of these and other studies.","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2019-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1212/NXI.0000000000000564","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43278260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}