Annals of Clinical and Translational Neurology最新文献

{"title":"Clinical Phenotyping of Long COVID Patients Evaluated in a Specialized Neuro-COVID Clinic.","authors":"Luana D Yamashita, Neel Desai, Abigail R Manning, Caitlin Pileggi, Sara Manning Peskin, Danielle K Sandsmark, Dennis L Kolson, Matthew K Schindler","doi":"10.1002/acn3.70031","DOIUrl":"https://doi.org/10.1002/acn3.70031","url":null,"abstract":"<p><strong>Objective: </strong>To report Long COVID characteristics and longitudinal courses of patients evaluated between 4/14/21-4/14/22 at the University of Pennsylvania Neurological COVID Clinic (PNCC), including clinical symptoms, neurological examination findings, and neurocognitive screening tests from a standardized PNCC neurological evaluation approach.</p><p><strong>Methods: </strong>This is a retrospective cross-sectional and longitudinal study in a single-center tertiary care academic center. Participants include 240 patients with documented evidence of a positive SARS-CoV-2 PCR or antibody test who underwent initial evaluation and 182 patients with longitudinal follow-up. Main outcomes evaluated are patient demographics, duration of illness prior to self-reported improvement, and cognitive testing results-including the Montreal Cognitive Assessment (version 8.2) (MoCA) and Oral Trail Making Test-B (OTMT-B).</p><p><strong>Results: </strong>The majority (73%) of patients did not require hospitalization for their acute COVID-19 symptoms. Frequent Long COVID complaints included headache (60%), dizziness/vertigo (40%), and disturbance of taste/smell (40%). Almost all (94%) patients reported cognitive symptoms, and over 30% of patients had abnormal scores on cognitive testing. Severe infection, fewer years of education level, and non-White race were found to be statistically associated with an increased likelihood of having abnormal scores on cognitive testing. Neuroimaging and clinical laboratory testing were largely not informative for patient care. Sixty-two percent of patients with follow-up visits self-reported improvement in their primary neurological complaint within 1 year of evaluation.</p><p><strong>Interpretation: </strong>Performance on standardized cognitive screening tests may not be consistent with frequently reported cognitive complaints in Long COVID patients. The most common clinical trajectory was self-reported improvement in the primary neurological symptom.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FGF14 GAA Intronic Expansion in Unsolved Adult-Onset Ataxia in the Care4Rare Canada Consortium.","authors":"Alexanne Cuillerier, Giulia F Del Gobbo, Layla Mackay, Erika Wall, Madeline Couse, Laura M McDonell, Mireille Cloutier, Matt C Danzi, Jodi Warman-Chardon, Pierre R Bourque, Oksana Suchowersky, Alan Mears, Luke Seldenthuis, Wendy Mears, Laura Larrigan, Alexandre White-Brown, Gerald Pfeffer, Dennis E Bulman, David Dyment, Kym M Boycott","doi":"10.1002/acn3.70016","DOIUrl":"https://doi.org/10.1002/acn3.70016","url":null,"abstract":"<p><strong>Background and objectives: </strong>Spinocerebellar ataxias (SCA) represent a clinically and genetically heterogeneous group of progressive neurodegenerative diseases with prominent cerebellar atrophy. Recently, a novel pathogenic repeat expansion in intron 1 of FGF14 was identified, causing adult-onset SCA (SCA27B). We aimed to determine the proportion of our unsolved adult-onset ataxia cohort harboring this expansion using several technologies, and to characterize the phenotypic presentation within our population.</p><p><strong>Methods: </strong>Individuals presenting with adult-onset ataxia (> 30 years old) and negative previous genetic testing were selected from the Care4Rare patient repository. Affected individuals were from all ethnicities, and 90% had a family history suggestive of dominant ataxia, representing 19 of the 23 families included. We used multiple tools (PCR, long-read genome sequencing and optical genome mapping (OGM)) to identify the pathogenic GAA repeat in FGF14.</p><p><strong>Results: </strong>Of the 23 families included in this study, 65.2% harbored a pathogenic GAA expansion in FGF14. Individuals of French-Canadian descent (FC) represented most of our cohort and had a 64.7% diagnostic yield. Affected individuals presented with gaze-evoked nystagmus, gait ataxia, cerebellar dysarthria, and early episodic features. The GAA expansion in FGF14 was visible by OGM in all individuals tested.</p><p><strong>Interpretation: </strong>Our diagnostic yield demonstrates this expansion may be the most common cause of adult-onset SCA in dominant families of FC ancestry. Our FC participants have a phenotype distinct from previously published FC patients, with gaze-evoked nystagmus being the most common eye anomaly. From a diagnostic standpoint, the pathogenic GAA repeat can be identified by OGM, but additional tests are required to complement the interpretation.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cerebello-Prefrontal Connectivity Underlying Cognitive Dysfunction in Spinocerebellar Ataxia Type 2.","authors":"Ami Kumar, Ruo-Yah Lai, Zena Fadel, Yicheng Lin, Pia Parekh, Rachel Griep, Ming-Kai Pan, Sheng-Han Kuo","doi":"10.1002/acn3.70028","DOIUrl":"https://doi.org/10.1002/acn3.70028","url":null,"abstract":"<p><strong>Objective: </strong>Spinocerebellar ataxia type 2 (SCA2) is a hereditary cerebellar degenerative disorder, with motor and cognitive symptoms. The constellation of cognitive symptoms due to cerebellar degeneration is named cerebellar cognitive affective syndrome (CCAS), which has increasingly been recognized to profoundly impact patients' quality of life; however, the brain circuits underlying these cognitive dysfunctions remain elusive.</p><p><strong>Methods: </strong>We utilized a novel technique, cerebello-cortical electroencephalogram (EEG), to investigate the resting-state functional connectivity in different frequency domains in 12 SCA2 patients and 24 age-matched controls. Given that the prefrontal cortex is strongly connected to the cerebellum, we studied the EEG connectivity between the cerebellum and the prefrontal cortex. We also conducted correlation analyses to explore the association between this connectivity and the severity of cognitive dysfunction, determined by CCAS scores.</p><p><strong>Results: </strong>Source-space spectral analysis differences between SCA2 patients and controls were observed in the cerebellum at the delta, theta, and beta frequencies. Functional connectivity between the posterior cerebellum and the prefrontal cortex revealed decreased theta and increased beta connectivity in SCA2 patients, with no differences in delta connectivity. Increased beta connectivity was unique to the prefrontal regions, not seen in the connectivity to the primary motor cortex or mid-temporal lobe. Interestingly, this beta connectivity correlated with CCAS scores in SCA2 patients.</p><p><strong>Conclusion: </strong>Our findings demonstrated that SCA2 patients have an increase in beta cerebello-prefrontal connectivity that correlates with cognitive performance. These findings suggest cerebello-cortical EEG could track circuit dysfunction underlying cognitive symptoms in SCA2, paving the way for developing targeted neuromodulation therapeutics.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subthalamic Nucleus Oscillatory Characteristics in Meige, Cervical Dystonia and Generalized Dystonia.","authors":"Zhu Guan-Yu, Yin Zi-Xiao, Chen Ying-Chuan, Timon Merk, Thomas Binns, Ma Ruo-Yu, Du Ting-Ting, Liu Yu-Ye, Xie Hu-Tao, Shi Lin, Yang An-Chao, Meng Fan-Gang, Wolf-Julian Neumann, Andrea A Kühn, Zhang Jian-Guo","doi":"10.1002/acn3.70040","DOIUrl":"https://doi.org/10.1002/acn3.70040","url":null,"abstract":"<p><strong>Objective: </strong>Deep brain stimulation offers a unique opportunity to record neural activity of the basal ganglia. While much work in dystonia has focused on the globus pallidus internus, expanding research to investigate subthalamic nucleus (STN) activity in various dystonia types is critical to provide a comprehensive understanding of dystonia pathophysiology.</p><p><strong>Methods: </strong>STN and cortex activity were recorded from 17 patients with cervical dystonia (CD), 19 with Meige syndrome, and 9 with generalized dystonia (GD) during the lead externalized period. We investigated local and network oscillatory characteristics, including power, bursts, and coherence. Additionally, we explored the relationship between these features and the severity of dystonic symptoms within each group and conducted a comparative analysis across the different dystonia types.</p><p><strong>Results: </strong>Peaks of low-frequency (4-13 Hz) and beta (14-30 Hz) power were present in the STN of all patients; most of the beta peaks are distributed in the high beta range (20-30 Hz). The CD and GD groups showed longer low-frequency bursts and greater high beta power in STN than the Meige group. Interestingly, the CD group showed stronger STN-cortex low-frequency coherence, while the GD group had stronger STN-cortex high beta coherence. Combined, low-frequency and beta features could predict symptom severity with a performance of 73% in the CD group and 82% in the GD group.</p><p><strong>Interpretation: </strong>Low-frequency and high-beta oscillations are present in the STN across all three types of dystonia. The distinct patterns may be associated with different underlying pathological mechanisms.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143778660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase 1, First-In-Human, Single-/Multiple-Ascending Dose Study of Iluzanebart in Healthy Volunteers.","authors":"Andreas Meier, Spyros Papapetropoulos, Andrew Marsh, Kelly Neelon, David Stiles, Ryan O'Mara, Evan A Thackaberry, Marco Colonna, Raj Rajagovindan","doi":"10.1002/acn3.70033","DOIUrl":"https://doi.org/10.1002/acn3.70033","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of iluzanebart, a fully human monoclonal antibody TREM2 (triggering receptor expressed on myeloid cells 2) agonist, after single- (SAD) and multiple-ascending-dose (MAD) administration.</p><p><strong>Methods: </strong>Healthy adult volunteers (N = 136) received intravenous placebo or iluzanebart 1-60 mg/kg (SAD) or 10-60 mg/kg (MAD) followed by serial pharmacokinetics and safety assessments. Safety assessments included adverse events (AEs), vital signs, electrocardiograms, and clinical laboratory evaluations. Pharmacokinetics were assessed through noncompartmental analysis. The study also included open-label cohorts (3, 10, 20, 40, 60 mg/kg SAD; 10, 20, 40 mg/kg MAD) for cerebrospinal fluid (CSF) collection for exploratory pharmacodynamic biomarker analysis.</p><p><strong>Results: </strong>Iluzanebart was safe and well tolerated following single and multiple doses of up to 60 mg/kg. Most AEs were mild and resolved spontaneously. The most frequently reported AE was pruritus. No serious AEs or investigational product-related clinically meaningful changes in vital signs, electrocardiograms, or laboratory assessments were reported. Iluzanebart serum exposure was related to dose, with a 29-day half-life that is supportive of monthly dosing and confirmed central nervous system (CNS) exposure (≈0.15% CSF-to-serum ratio). Durable and dose-dependent target engagement, evidenced by marked reductions in soluble TREM2 and increased soluble CSF1R (colony-stimulating factor 1 receptor) and osteopontin/SPP1 (secreted phosphoprotein 1) levels in CSF, was observed, indicating that iluzanebart changes microglial activity following single and repeat dosing.</p><p><strong>Interpretation: </strong>Iluzanebart demonstrated favorable safety, tolerability, pharmacokinetics, and pharmacological activity in the CNS, supporting further clinical development for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reconstitution of CXCR3⁺ CCR6⁺ Th17.1-Like T Cells in Response to Ofatumumab Therapy in Patients With Multiple Sclerosis.","authors":"Shu Yang, Tian-Xiang Zhang, Jia Liu, Zhirui Liu, Lijie Zhu, Yan-Yan Li, Bin Feng, Moli Fan, Fu-Dong Shi, Chao Zhang","doi":"10.1002/acn3.70042","DOIUrl":"https://doi.org/10.1002/acn3.70042","url":null,"abstract":"<p><strong>Background and objectives: </strong>Ofatumumab, a fully human anti-CD20 monoclonal antibody, is effective in reducing relapses and disability progression in patients with multiple sclerosis. This study aimed to examine immune profile changes associated with ofatumumab in a prospective cohort of Chinese patients with relapsing-remitting multiple sclerosis (RRMS).</p><p><strong>Methods: </strong>Seventeen RRMS patients were enrolled in this uncontrolled, prospective, observational cohort study (OMNISCIENCE study) and received regular subcutaneous ofatumumab treatments. Immune cell subsets were analyzed by single-cell mass cytometry at baseline and 6 months post-treatment. Peripheral blood monoclonal cells (PBMCs) from a separate cohort of treatment-naive RRMS patients were used for cytokine analysis through ex vivo flow cytometry.</p><p><strong>Results: </strong>Following ofatumumab treatment, B cells in peripheral blood remained depleted, with surviving cells predominantly consisting of antibody-secreting cells and transitional B cells. Increased proportions of NK cells and myeloid cells, particularly HLA-DR^hi intermediate monocytes, were observed, and FOXP3 and CTLA-4 expression on CD4⁺ T cells was upregulated. Notably, prior to the subsequent dose of ofatumumab, Th17.1-like CXCR3⁺CCR6⁺ memory CD4⁺ and CD8⁺ T cell clusters increased significantly, with a transient CD20 expression rebound. In vitro experiments further confirmed that ofatumumab reduced these Th17.1 cell subsets and related pro-inflammatory cytokines.</p><p><strong>Discussion: </strong>These findings suggest that ofatumumab impacts interactions among pathogenic B cells, T cells, and myeloid cells, with Th17.1 cells emerging as a potential direct target within T cells. Persistent and regular infusions of ofatumumab appear necessary to sustain clinical efficacy.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov identifier: NCT05414487.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF Tau Is a Biomarker of Hippocampal Injury in Cryptogenic New-Onset Refractory Status Epilepticus.","authors":"Yihui Goh, Yoonhyuk Jang, Soo Jean Shin, Soo Hyun Ahn, Su Yee Mon, Yoon Hee Shin, Kon Chu, Sang Kun Lee, Soon-Tae Lee","doi":"10.1002/acn3.70043","DOIUrl":"https://doi.org/10.1002/acn3.70043","url":null,"abstract":"<p><strong>Objective: </strong>Cryptogenic new-onset refractory status epilepticus (cNORSE) is a devastating condition characterized by the de novo onset of status epilepticus with unclear etiology. The identification of relevant early biomarkers in cNORSE is important to elucidate pathophysiology, aid clinical decision-making, and prognosticate outcomes in cNORSE.</p><p><strong>Methods: </strong>CSF samples were obtained within 7 days of NORSE onset from an adult cNORSE cohort in a national referral center in South Korea. Nineteen patients with cNORSE were studied: 9 were male (47.4%) and the median age was 35.0 [IQR: 27.0-54.3] years. CSF from 21 patients with other neurological diseases (atypical parkinsonism, postural orthostatic hypotension syndrome, epilepsy, and cerebellar ataxia) was used as controls. Proteomic analysis was conducted using the Olink platform, and potential biomarker candidates were correlated with clinical data and MRI findings.</p><p><strong>Results: </strong>Based on correlation analyses between proteomic data and clinical outcomes, total tau (t-tau) was selected as a potential biomarker. Patients with cNORSE had higher CSF t-tau levels than controls (p < 0.001). Early detection of high CSF t-tau was associated with the presence of hippocampal atrophy in the postacute phase of cNORSE (p = 0.044). The initial elevation of t-tau levels also correlated with a higher number of anti-seizure medications used (p = 0.031) and less improvement in Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores 1 month after NORSE onset (p = 0.066). T-tau levels were correlated with CSF pro-inflammatory cytokines/chemokines and mediators of neuronal damage.</p><p><strong>Interpretation: </strong>Elevated CSF t-tau levels detected early after cNORSE onset may be a useful marker of initial brain injury and predict subsequent hippocampal atrophy.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Phenotypes and Deep Intronic Variant Expand TH-Associated Dopa-Responsive Dystonia Spectrum.","authors":"Xiaosheng Zheng, Chenxin Ying, Nan Jin, Jinghong Ma, Xinhua Wan, Xunhua Li, Wei Luo","doi":"10.1002/acn3.70013","DOIUrl":"https://doi.org/10.1002/acn3.70013","url":null,"abstract":"<p><p>Approximately 20% of dopa-responsive dystonia (DRD) cases remain genetically unresolved. Using whole-genome sequencing, we identified two TH variants in a young DRD patient, including a novel deep intronic variant. Minigene assays confirmed that this variant causes aberrant splicing. The patient exhibited an atypical disease progression compared with typical TH-associated DRD cases, presenting with generalized dystonia, episodic hypotonia, Parkinsonism, and oromandibular dyskinesias. These findings, including the first known documented deep intronic TH variant, expand our understanding of TH-associated DRD's phenotypic and genotypic spectrum, aiding clinical evaluation.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Case of a 67-Year-Old Man With Memory Difficulties and Altered Sleep.","authors":"Wesley Peng, Borna Bonakdarpour","doi":"10.1002/acn3.70027","DOIUrl":"https://doi.org/10.1002/acn3.70027","url":null,"abstract":"","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitope Mapping of Anti-Neurofascin 155 Antibody in a Large Cohort of Autoimmune Nodopathy Patients.","authors":"Amina A Abdelhadi, Hidenori Ogata, Xu Zhang, Takumi Tashiro, Ryo Yamasaki, Jun-Ichi Kira, Noriko Isobe","doi":"10.1002/acn3.70036","DOIUrl":"https://doi.org/10.1002/acn3.70036","url":null,"abstract":"<p><strong>Objective: </strong>Autoimmune nodopathy (AN), a newly recognized disease entity, is an immune-mediated polyneuropathy involving autoantibodies against cell adhesion molecules located in nodes of Ranvier and paranodal regions, such as neurofascin 186 (NF186) and neurofascin 155 (NF155). The present study aimed to identify the epitopes for autoantibodies against NF155 in a large cohort of Japanese patients with anti-NF155 antibody-positive (anti-NF155+) AN.</p><p><strong>Methods: </strong>Human embryonic kidney 293 cells stably expressing NF155, NF186, or the third to fourth fibronectin type III domain region (Fn3-Fn4) of NF155, as well as cells transiently expressing Fn3, Fn4, or the shorter Fn3-Fn4 region of NF155, were developed. Western blotting and flow cytometric cell-based assay (CBA) analyses were performed to determine the expression levels of the proteins and identify their target epitopes in serum samples from 100 IgG4 anti-NF155+ patients, four non-IgG4 anti-NF155+ patients, and eight healthy controls.</p><p><strong>Results: </strong>The expression levels of NF186, NF155, Fn3-Fn4 of NF155, and the other truncation variants of NF155 were confirmed by western blotting and flow cytometric CBA. Flow cytometric CBA analysis showed that the autoantibodies in all 104 anti-NF155+ patients bound to Fn3-Fn4. No autoantibodies reacted with NF186, Fn4, or shorter Fn3-Fn4, although the autoantibodies in one IgG4 anti-NF155+ patient (1.0%) recognized Fn3 in addition to Fn3-Fn4. Western blotting analysis of representative samples generally reproduced the CBA results.</p><p><strong>Interpretation: </strong>The present study involving a large cohort of patients clarified that the primary epitope for anti-NF155 antibodies is located in the Fn3-Fn4 region, but not in the Fn3 or Fn4 domains alone.</p>","PeriodicalId":126,"journal":{"name":"Annals of Clinical and Translational Neurology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}