Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Multimodal Longitudinal Optical Imaging Reveals Optic Neuritis Preceding Retinal Pathology in Experimental Autoimmune Encephalomyelitis.","authors":"Raphael Raspe, Robert Günther, Ralf Uecker, Asylkhan Rakhymzhan, Friedemann Paul, Helena Radbruch, Raluca Aura Niesner, Anja Erika Hauser","doi":"10.1212/NXI.0000000000200338","DOIUrl":"10.1212/NXI.0000000000200338","url":null,"abstract":"<p><strong>Background and objectives: </strong>Inflammatory demyelinating diseases of the CNS, chief among them multiple sclerosis (MS), are a major cause of disability in young adults. Early manifestations of MS commonly involve visual dysfunction, which is often caused by optic neuritis and is accompanied by quantifiable structural changes of the anterior visual pathway. Retinal optical coherence tomography (OCT) has emerged as an important tool for clinical assessment of these structural alterations, but the underlying pathobiological mechanisms and temporal dynamics are yet poorly understood at a cellular level.</p><p><strong>Methods: </strong>Using the experimental autoimmune encephalomyelitis (EAE) model of MS in fluorescent reporter mouse strains for neuronal function and innate immune cells, we use a unique combination of retinal intravital 2-photon microscopy (2PM) and OCT. In this fashion, we elucidate the spatiotemporal interplay of functional and structural retinal changes over the course of 1 month after EAE induction, with histopathologic imaging validating main results.</p><p><strong>Results: </strong>While all mice display histologic signs of optic neuritis early after EAE induction and independently of motor symptom severity, retinal signs of neuronal stress and parenchymal immune activation spike well after clinical peak of disease, with no signs of lasting structural damage appearing within 1 month after EAE induction. Thus, local retinal endpoints appear to be functions of downstream axonal damage rather than of immediate immune activation directed at the retina. However, as early as 1 week after EAE induction, retinal 2PM can detect recruitment of perivascular immune cells towards the optic nerve (ON), providing the earliest sign of disease activity in otherwise clinically inconspicuous mice.</p><p><strong>Discussion: </strong>Our work identifies the recruitment of CX3CR1+ cells to the ON as an early sign of disease underlining the importance of combined structural and functional retinal imaging for the spatiotemporal characterization of neuroinflammatory and neurodegenerative processes. It further proposes retinal phagocyte orientation, morphology, and abundance as potential surrogate markers for neurodegenerative activity.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200338"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813868","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":"Reemerging Infectious Diseases and Neuroimmunologic Complications.","authors":"Avindra Nath, Dennis L Kolson","doi":"10.1212/NXI.0000000000200356","DOIUrl":"10.1212/NXI.0000000000200356","url":null,"abstract":"<p><p>During the past decade (and beyond), neurologists have become aware of the emergence, persistence, and consequences of some familiar and new infections affecting the nervous system. Even among the familiar CNS infections, such as herpes virus, polyoma virus/JC, influenza, arbovirus, and hepatitis, challenges remain in developing effective antiviral treatments and treatments of postinfection sequelae. With the changing environment and increased global travel, arthropod vectors that mediate zoonotic disease transmission have spread unfamiliar viruses such as West Nile virus, dengue, chikungunya, equine encephalitis, and Zika, among others. Although the global health impact of these diseases has not risen to that of COVID-19 and HIV, it is likely to dramatically increase with continued spread of transmission vectors and the emergence of new zoonotic animal-to-human diseases mediated by those transmission vectors. Furthermore, specific virus-targeting treatments or effective vaccines for arboviral infections are not yet available, and this represents a major challenge in limiting the morbidity of these infections. By contrast, HIV-1, a disease that originated by direct transmission from nonhuman primates to humans (as early as the 1930s), after many years of intense study, is now targeted by highly specific and effective antiviral drugs that can limit the spread of infection and extend human life and health in all populations. Even with these dramatic therapeutic effects of suppressing HIV replication, neurologic dysfunction (primarily cognitive impairment) affects significant numbers of persons living with HIV. This emphasizes not only the importance of treating the underlying infection but also developing treatments for legacy effects of the initial infection even after antiviral therapy. Notably, the rapid emergence of SARS-CoV-2 infection was met with rapid implementation of highly effective and specific antiviral therapies. This resulted in early and dramatic lowering of the morbidity and mortality of SARS-CoV-2 infection. Nonetheless, the postinfectious complications of SARS-CoV-2 infection (long COVID) are now among the more costly consequences of emerging zoonotic infections worldwide. Developing new antiviral therapies that can penetrate the CNS, vaccines, and therapies that target host immune responses and metabolic dysfunction will be necessary for management of infectious and postinfectious complications of established and emerging infections.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200356"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11658811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854874","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":"Proteomic Profiling and Pathophysiological Implications in Multiple Sclerosis.","authors":"Michael R Wilson, Ahmed Abdelhak","doi":"10.1212/NXI.0000000000200341","DOIUrl":"10.1212/NXI.0000000000200341","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200341"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11563563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624800","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":"Anti-IgLON5 Disease 10 Years Later: What We Know and What We Do Not Know.","authors":"Francesc Graus, Lidia Sabater, Carles Gaig, Ellen Gelpi, Alex Iranzo, Josep O Dalmau, Joan Santamaria","doi":"10.1212/NXI.0000000000200353","DOIUrl":"10.1212/NXI.0000000000200353","url":null,"abstract":"<p><p>Anti-IgLON5 disease was identified 10 years ago, thanks to the discovery of IgLON5 antibodies and the joint effort of specialists in sleep medicine, neuroimmunology, and neuropathology. Without this collaboration, it would have been impossible to untangle fundamental aspects of this disease. After the seminal description in 2014, today there is growing evidence that most patients present a chronic progressive course with gait instability, abnormal movements, bulbar dysfunction, and a sleep disorder characterized by nonrapid eye movement and REM parasomnias, and obstructive sleep apnea with stridor. Unlike other autoimmune encephalitides, the response to immunotherapy is suboptimal. Neuropathologic studies in patients with a prolonged clinical course showed a novel 3-repeat and 4-repeat neuronal tauopathy mainly involving the hypothalamus and tegmentum of the brainstem. The absence of tau deposits in the brain of patients who died early, the demonstration that IgLON5 antibodies cause an irreversible decrease in cell-surface levels of IgLON5, and a disorganization of the neuronal cytoskeleton suggest that the disease is primarily autoimmune and the tauopathy a secondary event. After a decade, we now know the disease much better, but important issues still need to be addressed. We have to gather more information on the natural course of the disease, develop better treatments, and identify robust predictors of outcome. More basic research is needed on the physiology of IgLON5, how antibodies disrupt its function, and the downstream effects leading to neurodegeneration. Finally, better designed passive transfer and active immunization models are needed to confirm the pathogenic effect of IgLON5 antibodies.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200353"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11666276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869686","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":"Ravulizumab and Efgartigimod in Myasthenia Gravis: A Real-World Study.","authors":"Frauke Stascheit, Carla Daiane Ferreira de Sousa, Annette Aigner, Malina Behrens, Christian W Keller, Luisa Klotz, Sophie Lehnerer, Maike Stein, Meret Herdick, Paolo Doksani, Lea M Gerischer, Sarah Hoffmann, Konstantinos Lazaridis, John Tzartos, Heinz Wiendl, Andreas Meisel, Jan D Lünemann","doi":"10.1212/NXI.0000000000200331","DOIUrl":"10.1212/NXI.0000000000200331","url":null,"abstract":"<p><strong>Background and objectives: </strong>Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab and the neonatal Fc receptor agonist efgartigimod have recently been approved for the treatment of acetylcholine receptor (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking.</p><p><strong>Methods: </strong>In a prospective, exploratory real-world study, we assessed clinical efficacy, safety, and biological effects of ravulizumab and efgartigimod treatment initiation. Myasthenia Gravis-Activities of Daily Living and Quantitative Myasthenia Gravis scores were used as clinical endpoints. Ab effector functions were determined by AChR-Ab-dependent complement activation and phagocytosis assays and systemic complement activation profiling.</p><p><strong>Results: </strong>We observed similar moderate short-term efficacy of ravulizumab and efgartigimod in achieving clinical improvement. Ravulizumab reduced systemic terminal complement activation, but neither treatment showed significant effects on complement pathways proximal to C5 or functional capacities of AChR-Abs. Both treatment modalities were well tolerated with no serious adverse events reported.</p><p><strong>Discussion: </strong>Clinical benefits obtained with ravulizumab and efgartigimod can be remarkably heterogeneous in daily clinical practice. Neither treatment relevantly changed effector functions of pathogenic AChR-Abs, supporting the concept that durable disease control in MG requires continuous administration of both fast-acting agents.</p><p><strong>Classification of evidence: </strong>This study provides Class III evidence that in AChR-Ab-positive patients with generalized MG, ravulizumab and efgartigimod provide comparable modest improvement in MG functional scales.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200331"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11604103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739874","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":"Selected Aspects of the Neuroimmunology of Cell Therapies for Neurologic Disease: Perspective.","authors":"Richard M Ransohoff","doi":"10.1212/NXI.0000000000200352","DOIUrl":"10.1212/NXI.0000000000200352","url":null,"abstract":"<p><p>Neurologic disease remains a cause of incalculable suffering, a formidable public health burden, and a wilderness of complex biology and medicine. At the same time, advances in basic science, technology, and the clinical development toolkit bring meaningful benefit for patients along with realistic hope for those whose conditions remain inadequately treated. This perspective focuses on cell-based therapies for neurologic disease, with particular emphasis on neuroimmunologic disorders and on the immunologic considerations of cell therapy for nonimmune conditions. I will consider the use of chimeric antigen receptor (CAR)-T effector cells and regulatory T-cell therapies for autoimmune conditions. I will briefly discuss the immune aspects of pluripotent stem cell (PSC)-derived neuronal therapies. With apologies for the omission, we do not discuss mesenchymal stem cells, glial progenitor cells, or CAR-NK cells, primarily for space limitations.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200352"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822213","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":"Patient-Reported Outcome Measures in NMDA Receptor Encephalitis.","authors":"Josephine Heine, Ole Jonas Boeken, Sophia Rekers, Katharina Wurdack, Harald Prüss, Carsten Finke","doi":"10.1212/NXI.0000000000200343","DOIUrl":"10.1212/NXI.0000000000200343","url":null,"abstract":"<p><strong>Background and objectives: </strong>The characteristics of persistent long-term symptoms and their contribution to subjective quality of life remain unclear in patients with NMDAR encephalitis. In this study, we aimed to evaluate postacute neuropsychiatric symptoms, subjective cognitive complaints, and disease coping mechanisms and identify predictors of health-related quality of life (HRQoL) after N-methyl-D-aspartate receptor (NMDAR) encephalitis.</p><p><strong>Methods: </strong>This cross-sectional observational study investigated patients with NMDAR encephalitis in the postacute phase. Psychometric scales included assessment of neuropsychiatric symptoms (i.e., fatigue, sleep, anxiety, and depressive symptoms), HRQoL, everyday independence, metamemory (i.e., self-rated ability, satisfaction, and use of strategies), and coping strategies (i.e., self-efficacy, disease-related coping, and stress management).</p><p><strong>Results: </strong>A total of 50 patients (mean age 26.0 ± 10.1 years, 86% female) participated at a median of 4.15 (range 0.3-30.3) years after symptom onset. Patients reported significantly increased levels of anxiety (Beck Anxiety Inventory: 10.5 ± 7.7 [mean ± SD], 95% CI [8.32-12.71], <i>p</i> < 0.001) and depressive (Beck Depression Inventory-II: 11.4 ± 7.7 [9.22-13.62], <i>p</i> = 0.001) symptoms compared with the normative population. Both sleep problems (Pittsburgh Sleep Quality Index: 5.8 ± 3.0 [4.98-6.66], <i>p</i> < 0.001) and motor and cognitive fatigue (Fatigue Scale for Motor and Cognitive Function: 50.5 ± 23.1 [42.5-58.4], <i>p</i> < 0.001) were significantly more prevalent. Moreover, lower self-rated memory ability (Multifactorial Memory Questionnaire score: 54.6 ± 8.5 [52.1-57.1], <i>p</i> = 0.004) was associated with greater reliance on compensatory strategies and memory aids (<i>r</i> = -0.41, <i>p</i> = 0.004). Patients used significantly fewer cognitive coping strategies, such as relativization (11.7 ± 4.7 [10.3-13.1], <i>p</i> = 0.001), while depressive coping prevailed (49.1 ± 15.5 [44.5-53.8], <i>p</i> < 0.001). It is important to note that HRQoL was predicted by self-reported affective symptoms, self-efficacy, and coping behaviors in multivariable regression analyses, but not by acute disease severity or postacute physical disability.</p><p><strong>Discussion: </strong>Our findings show that persistent neuropsychiatric and subjective cognitive concerns explain a large part of the reduced quality of life in patients with NMDAR encephalitis. These findings have important implications for a patient-centered postacute care and the role of disease coping strategies in the neurorehabilitation of autoimmune encephalitis.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200343"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818797","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":"Micro-RNA Signature in CSF Before and After Autologous Hematopoietic Stem Cell Transplantation for Multiple Sclerosis.","authors":"Ivan Pavlovic, Fredrik Axling, Faisal Hayat Nazir, Malin Müller, Anna Wiberg, Joachim Burman","doi":"10.1212/NXI.0000000000200345","DOIUrl":"10.1212/NXI.0000000000200345","url":null,"abstract":"<p><strong>Background and objectives: </strong>MicroRNAs (miRNAs) are regulators of gene expression and have been reported to be dysregulated in people with multiple sclerosis (pwMS). Autologous hematopoietic stem cell transplantation (aHSCT) is an immune-ablative treatment intervention for pwMS. Currently, it is unknown if aHSCT affects expression levels of miRNAs in CSF. We explored the ability of circulating miRNA to discriminate between pwMS and healthy controls (HCs) and investigated whether these miRNAs were affected by treatment with aHSCT.</p><p><strong>Methods: </strong>Using quantitative reverse transcription PCR, 87 miRNAs were analyzed in CSF samples of a discovery cohort (<i>baseline: 4 & HC: 4</i>). The top 22 miRNAs discriminating between pwMS and HCs were then analyzed in 187 CSF samples of a validation cohort (<i>pwMS: 50, HC: 32</i>). Samples, failing quality control or being follow-ups to baseline samples with quality control issues, were excluded from further analyses. The remaining 133 samples (<i>HC: 29, MS: baseline: 33, 1 year: 30, 2 years: 26, 3-5 years: 15</i>) were analyzed for expression of the top 22 miRNAs.</p><p><strong>Results: </strong>Twelve miRNAs were dysregulated in pwMS compared with HC (<i>q</i> < 0.05). Associations with clinical and analytical parameters were observed in relation to all 12 miRNAs; however, a cluster of 4 miRNAs (miR-16-5p, miR-21-5p, miR-150-5p, and miR-146a-5p) with strong correlations (<i>r</i> > 0.60, <i>p</i> < 0.001) with multiple parameters was identified. Of the 12 miRNAs, 8 were differentially expressed in pwMS with gadolinium-enhancing lesions at baseline and 4 by prior disease-modifying treatment class (<i>p</i> < 0.05). These 4 miRNAs correlated strongly with each other, decreased after aHSCT, and remained low throughout the follow-up period (<i>p</i> < 0.05). Target and pathway analysis of these revealed association with biological processes affecting cytokine production, inflammatory response, and regulation of myelin maintenance.</p><p><strong>Discussion: </strong>miRNAs are dysregulated in CSF from pwMS and particularly in patients with less effective treatments and/or higher inflammatory disease activity. A 4-miRNA signature with elevated expression of miR-16-5p, miR-21-5p, miR-150-5p, and miR-146a-5p was recurring in multiple analyses. After intervention with aHSCT, the expression levels approached the levels of the HCs, suggesting a potent treatment effect.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200345"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11655170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142847374","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":"The Discovery of Autoimmune Nodopathies and the Impact of IgG4 Antibodies in Autoimmune Neurology.","authors":"Luis Querol, Marinos C Dalakas","doi":"10.1212/NXI.0000000000200365","DOIUrl":"10.1212/NXI.0000000000200365","url":null,"abstract":"<p><p>In the past decade, significant progress has been made on the understanding of IgG4-mediated autoimmune diseases, of both the central and the peripheral CNS. In addition to the description of diverse antigenic targets, the description of IgG subclasses associated with specific pathogenic autoantibodies has provided useful insights into the pathophysiology and, more importantly, into the therapeutic implications of the autoantibody subclasses. This understanding has affected how myasthenia gravis, autoimmune encephalitis, and autoimmune neuropathies are treated. In the case of autoimmune neuropathies, the discovery of antigenic targets located at the node of Ranvier has led to the definition of a new diagnostic category, the autoimmune nodopathies, which differentiate them from the classical forms of Guillain-Barré syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. These neuropathies including those caused by autoantibodies targeting contactin-1, contactin-associated protein 1, and neurofascin are mainly, though not always exclusively, mediated by IgG4 antibodies, and respond to therapies similarly to other IgG4-mediated neurologic and non-neurologic diseases, providing evidence that not only the antigenic target but also the autoantibody subclass play a role in understanding both the disease pathophysiology and response to therapies. In this article, we describe the history and main findings on autoimmune nodopathies; highlight the particularities and similarities of IgG4-mediated neurologic diseases, including autoimmune nodopathies and neuromuscular junction and certain CNS disorders; elaborate on the unique functional properties of IgG4 in influencing their specific response to immunotherapies stressing the rationale of the most suitable present and future targeted therapies; and discuss how best to apply and monitor maintenance therapies for inducing disease stability in all IgG4 neurologic autoimmunities including the need for potential future biomarkers.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200365"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11649181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822202","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":"Broad Analysis of Serum and Intrathecal Antimicrobial Antibodies in Multiple Sclerosis Underscores Unique Role of Epstein-Barr Virus.","authors":"Florence Pache, Carolin Otto, Diana Wilken, Tatjana Lietzow, Katja Steinhagen, Evelin Grage-Griebenow, Patrick Schindler, Moritz Niederschweiberer, Brigitte Wildemann, Sven Jarius, Klemens Ruprecht","doi":"10.1212/NXI.0000000000200332","DOIUrl":"10.1212/NXI.0000000000200332","url":null,"abstract":"<p><strong>Background and objectives: </strong>There is a strong link between Epstein-Barr virus (EBV) and multiple sclerosis (MS), but the underlying mechanisms are unclear. Patients with MS typically have a polyspecific intrathecal production of immunoglobulin G (IgG), part of which is directed against various microbial antigens. In this study, we comprehensively analyzed seroprevalences and frequencies of an intrathecal IgG production to EBV compared with 10 other common microbes in patients with MS.</p><p><strong>Methods: </strong>Antibodies to EBV and to <i>Borrelia burgdorferi</i>, cytomegalovirus, herpes simplex virus type 1/2, measles virus, mumps virus, rubella virus, parvovirus B19, tick-borne encephalitis virus, <i>Toxoplasma gondii</i>, and varicella zoster virus (VZV) were determined in stored paired CSF and serum samples of 50 patients with MS. Intrathecal antimicrobial antibody production was assessed by calculating antibody indices (AIs) according to standard formula.</p><p><strong>Results: </strong>While 50 (100%) of 50 patients with MS were EBV seropositive, seroprevalences of all other 10 microbes were lower, ranging from 94% (VZV) to 6% (<i>Borrelia burgdorferi</i>). An intrathecal production of antimicrobial antibodies was detected in 102 (28%) of 370 AI determinations of patients who were seropositive to the respective antimicrobial antibodies but was practically absent in seronegative patients (2/187 [1%], <i>p</i> < 0.0001). The frequency of intrathecally produced antimicrobial antibodies among patients who were seropositive for the respective antibodies was roughly 40% for measles, rubella, mumps, and VZV and 70% for parvovirus B19. By contrast, the frequency of intrathecally produced EBV antibodies was low (10%) and, when related to their respective seroprevalences, lower than those of all other investigated microbes.</p><p><strong>Discussion: </strong>Despite the universal EBV seroprevalence, the frequency of intrathecally produced EBV antibodies in patients with MS is lower than that of other microbes, whose seroprevalences are lower than those of EBV. This seemingly paradoxical finding underscores the unique role of EBV in MS and could be explained by the hypothesis that B lineage cells responsible for intrathecal antibody production are primed during and through acute EBV infection to enter the CNS of patients with MS, that is, at a time point when EBV antibody-producing cells have not yet been generated and, therefore, are not yet available for entering the CNS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 1","pages":"e200332"},"PeriodicalIF":7.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11616972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739952","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}