Clinical and Experimental Neuroimmunology最新文献

{"title":"Aging and Neuroimmunological Disorders","authors":"Takuya Matsushita","doi":"10.1111/cen3.70016","DOIUrl":"https://doi.org/10.1111/cen3.70016","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 3","pages":"192-193"},"PeriodicalIF":0.0,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging and Multiple Sclerosis","authors":"Takuya Matsushita","doi":"10.1111/cen3.70015","DOIUrl":"https://doi.org/10.1111/cen3.70015","url":null,"abstract":"<p>Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease. While typically diagnosed in young adults, late-onset MS (LOMS, onset &gt; 50 years) is becoming increasingly recognized, presenting with distinct features such as higher rates of progressive onset and motor symptoms. With prolonged life expectancy and widespread use of disease-modifying therapies (DMTs), the population of aging individuals with MS is growing. Managing DMTs in this population is challenging, requiring the balancing of decreased relapse frequency against increased comorbidity and treatment risks. Discontinuation decisions are complex, as disease activity, including progression-independent of relapse activity (PIRA), can persist. Research, including ongoing trials, is evaluating the role of DMTs in preventing progression in older patients. Furthermore, aging involves biological processes such as immunosenescence, inflammaging (driven by cells with a senescence-associated secretory phenotype), and structural central nervous system changes such as enlarged perivascular spaces. These age-related alterations in immune and neurodegenerative pathways show significant overlap with MS pathophysiology. Understanding this intersection is crucial for optimizing clinical management in older MS patients and may identify novel targets for disease modification.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 3","pages":"208-213"},"PeriodicalIF":0.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782328","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}

{"title":"Pathogenic Roles of Age-Associated B Cells in Neuromyelitis Optica Spectrum Disorder","authors":"Eiichiro Amano,&nbsp;Wakiro Sato,&nbsp;Takashi Yamamura","doi":"10.1111/cen3.70012","DOIUrl":"https://doi.org/10.1111/cen3.70012","url":null,"abstract":"<div>\u0000 \u0000 <p>Age-associated B cells (ABCs), initially identified in aged mice, are a distinct B cell subset that plays crucial roles in autoimmune diseases through the production of autoantibodies, proinflammatory cytokines, and antigen presentation. Although a definitive set of markers for identifying ABCs has not yet been established, they are commonly characterized by the expression of CD11c, CD11b, and the transcription factor T-bet, along with reduced levels of CD21, either alone or in combination. ABC differentiation is driven by Toll-like receptor 7 (TLR7) signaling in conjunction with cytokines such as interleukin-21 (IL-21) and interferon-gamma (IFNγ). Importantly, ABCs expand in the blood or inflamed tissues and exhibit pathogenic functions in various autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, Crohn's disease, axial spondyloarthritis, Grave's disease, and multiple sclerosis. Recently, ABCs have been implicated in neuromyelitis optica spectrum disorder (NMOSD), a chronic inflammatory astrocytopathy mediated by anti-AQP4 antibody-producing B cells characterized by relapses and remissions. In the acute phase, CD21^lo B cells can differentiate into anti-AQP4 antibody-producing cells and expand in both cerebrospinal fluid and blood. In the chronic phase, an increased frequency of CD11c^hi B cells in the blood correlates with chronic neurological damage or brain injury. T peripheral helper type 1 cells, which produce IFNγ and IL-21, may support ABC differentiation in both phases. This review explores the role of ABCs in NMOSD, highlighting key studies that link ABC subsets to disease pathology. Understanding ABC-mediated mechanisms in NMOSD may open avenues for novel therapeutic strategies.</p>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 3","pages":"198-207"},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pathogenic Role of Age-Associated B Cells in Autoimmune Disorders and Myasthenia Gravis","authors":"Hiroyuki Akamine,&nbsp;Akiyuki Uzawa","doi":"10.1111/cen3.70011","DOIUrl":"https://doi.org/10.1111/cen3.70011","url":null,"abstract":"<p>Age-associated B cell (ABC) is a distinctive B cell subset characterized by CD11c and T-bet expression that accumulates with aging and in autoimmune conditions. This review summarizes current understanding of ABCs in the immunological function and autoimmune pathogenesis of autoimmune diseases, including myasthenia gravis (MG). ABCs arise when B cells are stimulated via B cell receptors and innate immune receptors (notably TLR7/9), in the presence of cytokines secreted by Th1 cells. ABCs behave as antigen-presenting cells, secrete inflammatory cytokines, and can differentiate into antibody-secreting cells. In autoimmune disorders, ABCs are thought to undergo expansion, efficiently present self-antigens to T cells, generate inflammatory mediators, and contribute to autoantibody production. Contemporary single-cell transcriptomic investigations of MG patients experiencing myasthenic crisis have identified clonally expanded ABC-like populations. These cells potentially contribute to MG pathogenesis through multiple mechanisms: enhancing T cell activation, sustaining autoreactive plasma cell development, and producing inflammatory cytokines. The increased number of ABCs in late-onset MG suggests a link between aging and autoimmunity. Targeting ABC development may be a useful treatment approach for antibody-mediated autoimmune diseases such as MG. Understanding ABCs helps explain how aging affects autoimmunity.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 3","pages":"194-197"},"PeriodicalIF":0.0,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782559","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}

{"title":"Correction to “Human Monocyte-Derived Microglia-Like (iMG) Cells: A Tool to Explore Microglial Dynamics”","authors":"","doi":"10.1111/cen3.70010","DOIUrl":"https://doi.org/10.1111/cen3.70010","url":null,"abstract":"<p>S. Kyuragi, S. Inamine, M. Ohgidani, and T. A. Kato, “Human Monocyte-Derived Microglia-Like (iMG) Cells: A Tool to Explore Microglial Dynamics,” <i>Clinical and Experimental Neuroimmunology</i> 15, no. 4 (2024): 222–227. https://doi.org/10.1111/cen3.12815.</p><p>The above article was published under the article category “Review Article.” This has been updated with the correct article category “Invited Review.”</p><p>We apologize for this error.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cen3.70010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144782803","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}

{"title":"Clinical and Radiological Advances in Autoimmune GFAP Astrocytopathy: Analysis of 387 Patients in Japan","authors":"Akio Kimura","doi":"10.1111/cen3.70007","DOIUrl":"https://doi.org/10.1111/cen3.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy (GFAP-A) is an autoimmune inflammatory central nervous system disease. Recent neuropathological findings indicate that GFAP-specific cluster of differentiation (CD)8⁺ T cells are likely the effectors of GFAP-A. Of 387 individuals in Japan identified as having GFAP-A, most presented with headache and/or fever followed by neurological symptoms including consciousness disturbance, urinary dysfunction, hyperreflexia, movement disorders, and papilledema. Sixteen (5.9%) of the 270 GFAP-A patients tested had coexisting antibodies. Cerebrospinal fluid (CSF) examination revealed lymphocytic pleocytosis and increased protein levels. Moreover, transiently increased CSF adenosine deaminase, decreased glucose, and positive oligoclonal band results were sometimes observed. Brain magnetic resonance imaging (MRI) occasionally showed T2-hyperintensity lesions. Linear perivascular radial gadolinium-enhancement patterns were observed and may be an imaging hallmark of GFAP-A. Spinal cord MRI sometimes exhibited T2-hyperintensity spinal cord lesions, most of which were longitudinally extensive. Most patients were treated with immunotherapies, including intravenous methylprednisolone pulse therapy with or without intravenous immunoglobulin therapy and/or plasma exchange; this was followed by oral corticosteroid therapy, which was gradually tapered. Some refractory patients received second-line immunotherapies including rituximab or cyclophosphamide. In 203 patients with follow-up ≥ 6 months, the median modified Rankin scale score at last follow-up was 1 (range: 0–6); however, 44 patients (21.7%) had scores of 3 or greater, and six patients died. The most common neurological finding at last follow-up was cognitive dysfunction, followed by urinary dysfunction; the recurrence rate was 10.5%. CSF GFAP-immunoglobulin G should be examined in patients who present with these characteristic clinical and radiological features.</p>\u0000 <p>\u0000 <b>Trial Registration:</b> Autoimmune GFAP astrocytopathy registry (UMIN: 000054387).</p>\u0000 </div>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 2","pages":"174-187"},"PeriodicalIF":0.0,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Mysteries of Rare Neuroimmunological Disorders","authors":"Yoshihisa Yamano","doi":"10.1111/cen3.70009","DOIUrl":"https://doi.org/10.1111/cen3.70009","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 2","pages":"148"},"PeriodicalIF":0.0,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmune cerebellar ataxia: An overlooked, but treatable, neuroimmune condition","authors":"Hiroaki Yaguchi,&nbsp;Akihiko Kudo,&nbsp;Ichiro Yabe","doi":"10.1111/cen3.70004","DOIUrl":"https://doi.org/10.1111/cen3.70004","url":null,"abstract":"<p>Autoimmune cerebellar ataxia (ACA) is a condition in which the cerebellum is the primary location of inflammation due to autoimmune encephalitis caused by neuroimmune conditions. Although ACA is rare, it remains an important differential diagnosis, distinct from other neurodegenerative conditions, such as multiple system atrophy. An accurate diagnosis requires the integration of clinical history, blood tests, cerebrospinal fluid analysis, magnetic resonance imaging and malignancy screening. Over 30 neural antibodies associated with ACA have been reported as diagnostic biomarkers. The clinical profile of frequently reported antibodies, such as anti-Yo and anti-GAD, are well-defined, although that of rarer antibodies remain unclear. Cell-based assays are the standard method for detecting most neural antibodies, but testing for a wide range of antibodies is costly. Immunoblots assays and tissue-based assays are useful for screening. Further investigations into clinical profiles and advancements in screening methods are required to identify neural antibodies. ACA should not be overlooked, due to its treatable nature. Acute phase treatments, such as intravenous methylprednisolone and immunoglobulin, plasma exchange, and rituximab, are effective. Maintenance therapy using steroids and/or immunosuppressants is used to prevent relapse and progression. However, maintenance therapy requires individualized decisions due to limited clinical evidence. Additionally, treatment responses might vary depending on the type of neural antibody. In the future, the development of biomarkers and improved autoantibody testing methods is important to develop novel therapies and optimal immunotherapy for patients with ACA.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 2","pages":"161-173"},"PeriodicalIF":0.0,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis and multiple sclerosis: Viral strategies and their implications","authors":"Makoto Nakashima,&nbsp;Yoshihisa Yamano","doi":"10.1111/cen3.70001","DOIUrl":"https://doi.org/10.1111/cen3.70001","url":null,"abstract":"<p>Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic inflammatory disease of the central nervous system (CNS), particularly affecting the spinal cord, and is caused by HTLV-1 infection. The biased geographic distribution of HTLV-1-infected individuals facilitated the early identification of a causal relationship between HTLV-1 infection and related diseases soon after the discovery of the virus. In contrast, such a relationship would have been challenging to establish without this geographic clustering. Similarly, Epstein–Barr virus (EBV), which infects ~95% of the global population, has recently been implicated in the pathogenesis of multiple sclerosis (MS), another chronic inflammatory CNS disease. Advances in seroepidemiology, immunology, genomics, and biomarker research in large MS cohorts have shed light on EBV's critical role in disease development. These insights provide a framework for understanding the molecular mechanisms underlying both MS and HAM/TSP, which remain incompletely elucidated. In this review, we compare HTLV-1 with EBV, focusing on their shared strategies for establishing long-term latency in the host and their roles in CNS inflammation. By analyzing the relationship between HAM/TSP and MS through virological and molecular biological perspectives, we propose that both conditions may represent chronic inflammatory diseases of the CNS triggered by viral infections. This hypothesis offers a novel perspective on the pathogenesis of these diseases. Finally, we discuss current challenges and future directions in the treatment and prevention of HAM/TSP and MS.</p>","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 2","pages":"149-160"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A thank you note to our reviewers","authors":"","doi":"10.1111/cen3.12832","DOIUrl":"https://doi.org/10.1111/cen3.12832","url":null,"abstract":"","PeriodicalId":10193,"journal":{"name":"Clinical and Experimental Neuroimmunology","volume":"16 1","pages":"84"},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143455668","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}