Chitinase-3-like protein 1 (CHI3L1), secreted by immune cells, plays a key role in modulating immune responses. Syndecan-1 (SDC-1), a cell surface heparan sulfate proteoglycan, is involved in the regulation of inflammation. This study aimed to evaluate whether CHI3L1 and soluble SDC-1 (sSDC-1) act as potential diagnostic targets in patients with relapsing-remitting multiple sclerosis (RRMS).
Methods
sSDC-1 and CHI3L1 levels were quantified using enzyme-linked immunosorbent assay (ELISA) in cerebrospinal fluid (CSF) samples collected from a cohort of 39 newly diagnosed patients with relapsing-remitting multiple sclerosis (RRMS) and 32 disease controls diagnosed with idiopathic intracranial hypertension (IIH).
Results
No significant difference was observed in CSF sSDC-1 levels between the RRMS and IIH groups. However, CSF CHI3L1 levels were significantly lower in patients with RRMS compared to those with IIH.
Conclusion
The present findings do not provide clear evidence supporting a diagnostic role for CSF levels of sSDC-1 or CHI3L1 in MS.
{"title":"Pilot analysis of Chitinase-3-like protein 1 and soluble Syndecan-1 CSF levels as potential biomarkers in relapsing-remitting multiple sclerosis","authors":"Firdevs Uluc , Dursun Ceylan , Sule Aydin Turkoglu","doi":"10.1016/j.jneuroim.2025.578836","DOIUrl":"10.1016/j.jneuroim.2025.578836","url":null,"abstract":"<div><h3>Background</h3><div>Chitinase-3-like protein 1 (CHI3L1), secreted by immune cells, plays a key role in modulating immune responses. Syndecan-1 (SDC-1), a cell surface heparan sulfate proteoglycan, is involved in the regulation of inflammation. This study aimed to evaluate whether CHI3L1 and soluble SDC-1 (sSDC-1) act as potential diagnostic targets in patients with relapsing-remitting multiple sclerosis (RRMS).</div></div><div><h3>Methods</h3><div>sSDC-1 and CHI3L1 levels were quantified using enzyme-linked immunosorbent assay (ELISA) in cerebrospinal fluid (CSF) samples collected from a cohort of 39 newly diagnosed patients with relapsing-remitting multiple sclerosis (RRMS) and 32 disease controls diagnosed with idiopathic intracranial hypertension (IIH).</div></div><div><h3>Results</h3><div>No significant difference was observed in CSF sSDC-1 levels between the RRMS and IIH groups. However, CSF CHI3L1 levels were significantly lower in patients with RRMS compared to those with IIH.</div></div><div><h3>Conclusion</h3><div>The present findings do not provide clear evidence supporting a diagnostic role for CSF levels of sSDC-1 or CHI3L1 in MS.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578836"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Serum glial fibrillary acidic protein (sGFAP) is increasingly studied as a biomarker of astroglial injury, but comparative data between ultra-sensitive analytical platforms are limited. This study evaluated the agreement between the newly developed VEUS technology and the established single-molecule array (SIMOA) method.
Methods
A single-centre retrospective analysis was conducted at the Department of Neurology, University Hospital Ostrava. Patients ≥18 years with relapsing-remitting multiple sclerosis, non-inflammatory neurological disorders, or symptomatic controls were included. sGFAP levels were measured using the SIMOA GFAP Advantage PLUS Kit (Quanterix) and the Duplex RUO Kit (GFAP/UCH-L1) (VEUDx, EZDiatech). Method comparison included Spearman correlation, Passing–Bablok regression, and Bland–Altman analysis. Outliers were removed using Tukey's IQR rule.
Results
Fifty-six patients (78.6 % women) were included. SIMOA reported markedly higher sGFAP concentrations (median 110.5 ng/L, IQR 83.2–176) compared with VEUS (median 6.13 ng/L, IQR 3.88–6.87). No significant correlation was observed between platforms (r = 0.02, p = 0.89). Passing–Bablok regression demonstrated a near-zero slope, indicating absent linear association. Bland–Altman analysis showed proportional bias, with VEUS measuring on average 21 % of SIMOA values and increasing divergence at higher concentrations.
Conclusion
These results do not support substituting sGFAP measurements between VEUS and SIMOA assays.
血清胶质原纤维酸性蛋白（sGFAP）作为星形胶质细胞损伤的生物标志物被越来越多地研究，但超灵敏分析平台之间的比较数据有限。本研究评估了新开发的VEUS技术与已建立的单分子阵列（SIMOA）方法之间的一致性。方法：在俄斯特拉发大学医院神经内科进行单中心回顾性分析。患者≥18年复发缓解型多发性硬化症，非炎症性神经系统疾病，或症状对照。使用SIMOA GFAP Advantage PLUS Kit （Quanterix）和Duplex RUO Kit (GFAP/UCH-L1) （VEUDx, EZDiatech）测量sGFAP水平。方法比较采用Spearman相关、Passing-Bablok回归、Bland-Altman分析。使用Tukey的IQR规则去除异常值。结果：共纳入56例患者（78.6%为女性）。SIMOA报告的sGFAP浓度（中位数为110.5 ng/L， IQR为83.2-176）明显高于VEUS（中位数为6.13 ng/L， IQR为3.88-6.87）。平台间无显著相关性（r = 0.02, p = 0.89）。passingbablok回归显示斜率接近于零，表明不存在线性关联。Bland-Altman分析显示出比例偏差，VEUS平均测量SIMOA值的21%，且浓度越高，差异越大。结论：这些结果不支持在VEUS和SIMOA测定之间替代sGFAP测定。
{"title":"Comparison of SIMOA and VEUS technologies for serum glial fibrillary acidic protein measurement","authors":"Radovan Bunganic , Kamila Zondra Revendova , Pavel Hradilek , Pavlina Kusnierova","doi":"10.1016/j.jneuroim.2025.578825","DOIUrl":"10.1016/j.jneuroim.2025.578825","url":null,"abstract":"<div><h3>Introduction</h3><div>Serum glial fibrillary acidic protein (sGFAP) is increasingly studied as a biomarker of astroglial injury, but comparative data between ultra-sensitive analytical platforms are limited. This study evaluated the agreement between the newly developed VEUS technology and the established single-molecule array (SIMOA) method.</div></div><div><h3>Methods</h3><div>A single-centre retrospective analysis was conducted at the Department of Neurology, University Hospital Ostrava. Patients ≥18 years with relapsing-remitting multiple sclerosis, non-inflammatory neurological disorders, or symptomatic controls were included. sGFAP levels were measured using the SIMOA GFAP Advantage PLUS Kit (Quanterix) and the Duplex RUO Kit (GFAP/UCH-L1) (VEUDx, EZDiatech). Method comparison included Spearman correlation, Passing–Bablok regression, and Bland–Altman analysis. Outliers were removed using Tukey's IQR rule.</div></div><div><h3>Results</h3><div>Fifty-six patients (78.6 % women) were included. SIMOA reported markedly higher sGFAP concentrations (median 110.5 ng/L, IQR 83.2–176) compared with VEUS (median 6.13 ng/L, IQR 3.88–6.87). No significant correlation was observed between platforms (<em>r</em> = 0.02, <em>p</em> = 0.89). Passing–Bablok regression demonstrated a near-zero slope, indicating absent linear association. Bland–Altman analysis showed proportional bias, with VEUS measuring on average 21 % of SIMOA values and increasing divergence at higher concentrations.</div></div><div><h3>Conclusion</h3><div>These results do not support substituting sGFAP measurements between VEUS and SIMOA assays.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578825"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-25DOI: 10.1016/j.jneuroim.2025.578821
Merna Wagdy , Abeer A. Ibrahim , Alaa M. Yahia, Rola M. Maher, Afaf Hany Abo-Elwafa, Alyaa Salah, Yasmin M. Heikal
Alzheimer's disease (AD) is a progressive neurodegenerative disorder identified by cognitive decline, memory loss, and behavioral changes, affecting approximately 50 million people worldwide. Genetic predisposition, environmental variables, and aging all play a role in the development of AD. Current therapeutic approaches primarily focus on alleviating symptoms through drugs such as donepezil and memantine. However, these treatments offer limited efficacy and may be accompanied by adverse effects. In contrast, natural therapies derived from algae present a promising alternative. Microalgae, including Chlorella and Spirulina, and macroalgae such as Fucus vesiculosus, Ecklonia cava, Sargassum, Laminaria japonica, and Fucus species, are rich in bioactive molecules having antioxidant and anti-inflammatory characteristics. These substances demonstrated potential in addressing the pathological features of AD, such as oxidative stress and neuroinflammation. Furthermore, advances in biotechnological tools like CRISPR-Cas9 gene editing are poised to enhance the efficacy of these natural therapies by targeting and modifying disease-associated genes. This review aims to bridge the fields of neurobiotechnology and marine bioresources by examining the synergistic potential of algal compounds and gene-editing strategies in combating Alzheimer's disease. Algal-derived compounds are utilized in pharmaceuticals, nutraceuticals, and dietary supplements, and may offer neuroprotective benefits that could aid in the prevention or treatment of AD.By integrating insights from molecular biology, pharmacology, and genomics, we seek to illuminate a novel, multidisciplinary framework for future therapeutic innovation.
{"title":"Neurobiotech innovative strategies targeting Alzheimer's disease through therapeutic micro and macroalgae potentials","authors":"Merna Wagdy , Abeer A. Ibrahim , Alaa M. Yahia, Rola M. Maher, Afaf Hany Abo-Elwafa, Alyaa Salah, Yasmin M. Heikal","doi":"10.1016/j.jneuroim.2025.578821","DOIUrl":"10.1016/j.jneuroim.2025.578821","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a progressive neurodegenerative disorder identified by cognitive decline, memory loss, and behavioral changes, affecting approximately 50 million people worldwide. Genetic predisposition, environmental variables, and aging all play a role in the development of AD. Current therapeutic approaches primarily focus on alleviating symptoms through drugs such as donepezil and memantine. However, these treatments offer limited efficacy and may be accompanied by adverse effects. In contrast, natural therapies derived from algae present a promising alternative. Microalgae, including Chlorella and Spirulina, and macroalgae such as <em>Fucus vesiculosus</em>, <em>Ecklonia cava</em>, Sargassum, <em>Laminaria japonica</em>, and Fucus species, are rich in bioactive molecules having antioxidant and anti-inflammatory characteristics. These substances demonstrated potential in addressing the pathological features of AD, such as oxidative stress and neuroinflammation. Furthermore, advances in biotechnological tools like CRISPR-Cas9 gene editing are poised to enhance the efficacy of these natural therapies by targeting and modifying disease-associated genes. This review aims to bridge the fields of neurobiotechnology and marine bioresources by examining the synergistic potential of algal compounds and gene-editing strategies in combating Alzheimer's disease. Algal-derived compounds are utilized in pharmaceuticals, nutraceuticals, and dietary supplements, and may offer neuroprotective benefits that could aid in the prevention or treatment of AD.By integrating insights from molecular biology, pharmacology, and genomics, we seek to illuminate a novel, multidisciplinary framework for future therapeutic innovation.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578821"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Emerging evidence suggests that imbalanced T-cell activity and immune dysfunction may contribute to migraine pathogenesis. However, the specific immune pathways remain unclear, particularly the role of B cells. To explore B-cell–related mechanisms, this study focused on two key members of the tumor necrosis factor (TNF) family, namely B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL), which play critical roles in B-cell survival and regulation. This study examined BAFF and APRIL expression in peripheral blood samples from migraine patients during pre-ictal, ictal, and post-ictal phases (n = 9) and in healthy controls (n = 9). BAFF levels increased during the ictal phase (p = 0.011) and declined in the post-ictal phase, whereas APRIL remained consistently downregulated relative to controls. The divergent patterns of BAFF and APRIL reveal a novel B-cell–related immune signature that may contribute to migraine pathogenesis. These preliminary findings support further studies to confirm these patterns and investigate the functional role of the BAFF–APRIL pathway in migraine.
{"title":"Exploratory analysis of B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) across migraine phases","authors":"Nisha Smithi , Pooja Singh , Swathika Rajendran , Harini Purushothaman , Ameena Bee , Vishnupriya Gurumoorthy Mani , Sowmiya Mari , Deepa Avadhani , Rajesh Kumar Gandhirajan , Murugesan Arumugam","doi":"10.1016/j.jneuroim.2025.578833","DOIUrl":"10.1016/j.jneuroim.2025.578833","url":null,"abstract":"<div><div>Emerging evidence suggests that imbalanced T-cell activity and immune dysfunction may contribute to migraine pathogenesis. However, the specific immune pathways remain unclear, particularly the role of B cells. To explore B-cell–related mechanisms, this study focused on two key members of the tumor necrosis factor (TNF) family, namely B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL), which play critical roles in B-cell survival and regulation. This study examined BAFF and APRIL expression in peripheral blood samples from migraine patients during pre-ictal, ictal, and post-ictal phases (<em>n</em> = 9) and in healthy controls (n = 9). BAFF levels increased during the ictal phase (<em>p</em> = 0.011) and declined in the post-ictal phase, whereas APRIL remained consistently downregulated relative to controls. The divergent patterns of BAFF and APRIL reveal a novel B-cell–related immune signature that may contribute to migraine pathogenesis. These preliminary findings support further studies to confirm these patterns and investigate the functional role of the BAFF–APRIL pathway in migraine.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578833"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-28DOI: 10.1016/j.jneuroim.2025.578823
Nicola Salvatore Orefice , Roberta Amoriello , Olfa Maghrebi , Chiara Ballerini , Giovanni Baldi , Roberta Arpino , Marianna Abate , Silvia Zappavigna , Luisa Pastò , Maria Pia Amato , Michele Caraglia , Clara Ballerini
Introduction
Multiple Sclerosis (MS) is an autoimmune, demyelinating, inflammatory disorder. The anti-CD20 monoclonal antibody ocrelizumab targets B cells, effectively controlling the disease. MicroRNAs (miRNAs), small molecules modulating immune responses and neuroinflammation, may serve as biomarkers for disease progression, though the impact of anti-CD20 remains unclear. We hereby selected three miRNAs of interest for their relevance in experimental autoimmune encephalomyelitis (EAE) and MS, miR-124a-3p, miR-125b-5p, and miR-223-3p.
Methods
We examined these miRNAs in the spinal cord of EAE mice treated with a nanoformulation of anti-CD20 and in 23 MS patients' serum (19 relapsing-remitting [RR] and 4 primary-progressive [PP]) before (T0) and after six months (T6) of ocrelizumab, alongside with serum cytokines and chemokines.
Results
We found reduced (*p = 0.045) miR-223-3p in nano-anti-CD20-treated mice and in patients (*p = 0.030) with inactive MS. RRMS showed varying miRNA expression, while PPMS exhibited reduced (*p = 0.029) miR-124a-3p at T6. CXCL10 was elevated (*p = 0.024) in patients with active MS. Overall, six cytokines increased at T6, with interleukin 6 (IL6) negatively correlating with miR-223-3p. Gene analysis showed that IL6 gene is among miRNAs' targets, alongside inflammatory pathways.
Conclusions
This is the first study to compare miR-124a-3p, miR-125b-5p, and miR-223-3p in both EAE and MS patients undergoing anti-CD20 therapy, suggesting subtype-specific molecular responses, identifying miR-223-3p as a potential biomarker of treatment response, and highlighting immune regulatory pathways as key mechanisms linking these miRNAs to disease progression and therapy outcomes.
{"title":"Early response in cytokine and miR-124a, -125b, -223 expression to anti-CD20 in Multiple Sclerosis and its animal model – a preliminary analysis","authors":"Nicola Salvatore Orefice , Roberta Amoriello , Olfa Maghrebi , Chiara Ballerini , Giovanni Baldi , Roberta Arpino , Marianna Abate , Silvia Zappavigna , Luisa Pastò , Maria Pia Amato , Michele Caraglia , Clara Ballerini","doi":"10.1016/j.jneuroim.2025.578823","DOIUrl":"10.1016/j.jneuroim.2025.578823","url":null,"abstract":"<div><h3>Introduction</h3><div>Multiple Sclerosis (MS) is an autoimmune, demyelinating, inflammatory disorder. The anti-CD20 monoclonal antibody ocrelizumab targets B cells, effectively controlling the disease. MicroRNAs (miRNAs), small molecules modulating immune responses and neuroinflammation, may serve as biomarkers for disease progression, though the impact of anti-CD20 remains unclear. We hereby selected three miRNAs of interest for their relevance in experimental autoimmune encephalomyelitis (EAE) and MS, miR-124a-3p, miR-125b-5p, and miR-223-3p.</div></div><div><h3>Methods</h3><div>We examined these miRNAs in the spinal cord of EAE mice treated with a nanoformulation of anti-CD20 and in 23 MS patients' serum (19 relapsing-remitting [RR] and 4 primary-progressive [PP]) before (T0) and after six months (T6) of ocrelizumab, alongside with serum cytokines and chemokines.</div></div><div><h3>Results</h3><div>We found reduced (*<em>p</em> = 0.045) miR-223-3p in nano-anti-CD20-treated mice and in patients (*<em>p</em> = 0.030) with inactive MS. RRMS showed varying miRNA expression, while PPMS exhibited reduced (*<em>p</em> = 0.029) miR-124a-3p at T6. CXCL10 was elevated (*<em>p</em> = 0.024) in patients with active MS. Overall, six cytokines increased at T6, with interleukin 6 (IL6) negatively correlating with miR-223-3p. Gene analysis showed that IL6 gene is among miRNAs' targets, alongside inflammatory pathways.</div></div><div><h3>Conclusions</h3><div>This is the first study to compare miR-124a-3p, miR-125b-5p, and miR-223-3p in both EAE and MS patients undergoing anti-CD20 therapy, suggesting subtype-specific molecular responses, identifying miR-223-3p as a potential biomarker of treatment response, and highlighting immune regulatory pathways as key mechanisms linking these miRNAs to disease progression and therapy outcomes.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578823"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145677888","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-28DOI: 10.1016/j.jneuroim.2025.578803
Masatoshi Hayashi
Myasthenia gravis (MG) is a signaling disorder caused by immune abnormalities at the neuromuscular junction, resulting in symptoms such as muscle weakness and fatigue. Groundbreaking research since the 1970s has revealed the pathophysiology of this disease to be a T cell-dependent, B cell-associated antibody-producing disease. Half a century ago, many patients died of the disease, Today, the mortality rate has declined with many patients achieving remission. Here, I review MG pathophysiology, issues in treatment considerations specific to childhood and adolescence, and examine how racial, cultural, and geographic differences impact the clinical phenotype and treatment practices in childhood-onset MG across East Asia and Western Europe.
{"title":"Diversity of childhood-onset myasthenia gravis: pathophysiology and treatment","authors":"Masatoshi Hayashi","doi":"10.1016/j.jneuroim.2025.578803","DOIUrl":"10.1016/j.jneuroim.2025.578803","url":null,"abstract":"<div><div>Myasthenia gravis (MG) is a signaling disorder caused by immune abnormalities at the neuromuscular junction, resulting in symptoms such as muscle weakness and fatigue. Groundbreaking research since the 1970s has revealed the pathophysiology of this disease to be a T cell-dependent, B cell-associated antibody-producing disease. Half a century ago, many patients died of the disease, Today, the mortality rate has declined with many patients achieving remission. Here, I review MG pathophysiology, issues in treatment considerations specific to childhood and adolescence, and examine how racial, cultural, and geographic differences impact the clinical phenotype and treatment practices in childhood-onset MG across East Asia and Western Europe.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578803"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145617639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-01DOI: 10.1016/j.jneuroim.2025.578822
María Agustina Piedrabuena , Mariano Marrodan , María Agustina Zárate , Marcela Fiol , María Celica Ysrraelit , Jorge Correale
Background
Neuromyelitis optica spectrum disorder (NMOSD) encompasses inflammatory demyelinating CNS conditions. Patients negative for aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) antibodies are classified as double seronegative (DN).
Objective
To characterize and compare the clinical, radiological, and therapeutic profiles of DN, AQP4-IgG+, and MOG-IgG+ patients.
Methods
Retrospective analysis of patients meeting 2015 NMOSD criteria, grouped by serostatus (AQP4-IgG+, MOG-IgG+, and DN). Demographic, clinical, and imaging data were compared.
Results
We analyzed 111 patients: 64 AQP4-IgG+, 31 DN, and 16 MOG-IgG+. At onset, AQP4-IgG+ patients were older than DN and MOG-IgG+ (49 ± 14 vs 41 ± 12 vs 35 ± 12 years, p < 0.0001). DN had more relapses in the first two years (p = 0.02) and higher EDSS (p < 0.001). Myelitis was common in DN and AQP4-IgG+, while optic neuritis in MOG-IgG+. Relapse rates were highest in AQP4-IgG+ (p < 0.001). Oligoclonal bands were more common in DN (39 %) than in AQP4-IgG+ (27.7 %) and MOG-IgG+ (25 %)(p < 0.0001). Area postrema lesions were more frequent in DN (p = 0.02). Rituximab was mainly used in AQP4-IgG+ and DN (p < 0.001), with lower failure in DN (4.8 % vs 18 %).
Conclusion
DN NMOSD shows distinct features but comparable disability to AQP4-IgG+ individuals. Conventional immunosuppressants seem effective, though further research is needed to clarify mechanisms and optimize treatment strategies.
{"title":"Characterizing double seronegative neuromyelitis optica spectrum disorder: A distinct subgroup or part of the continuum?","authors":"María Agustina Piedrabuena , Mariano Marrodan , María Agustina Zárate , Marcela Fiol , María Celica Ysrraelit , Jorge Correale","doi":"10.1016/j.jneuroim.2025.578822","DOIUrl":"10.1016/j.jneuroim.2025.578822","url":null,"abstract":"<div><h3>Background</h3><div>Neuromyelitis optica spectrum disorder (NMOSD) encompasses inflammatory demyelinating CNS conditions. Patients negative for aquaporin-4 (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG-IgG) antibodies are classified as double seronegative (DN).</div></div><div><h3>Objective</h3><div>To characterize and compare the clinical, radiological, and therapeutic profiles of DN, AQP4-IgG+, and MOG-IgG+ patients.</div></div><div><h3>Methods</h3><div>Retrospective analysis of patients meeting 2015 NMOSD criteria, grouped by serostatus (AQP4-IgG+, MOG-IgG+, and DN). Demographic, clinical, and imaging data were compared.</div></div><div><h3>Results</h3><div>We analyzed 111 patients: 64 AQP4-IgG+, 31 DN, and 16 MOG-IgG+. At onset, AQP4-IgG+ patients were older than DN and MOG-IgG+ (49 ± 14 vs 41 ± 12 vs 35 ± 12 years, <em>p</em> < 0.0001). DN had more relapses in the first two years (<em>p</em> = 0.02) and higher EDSS (<em>p</em> < 0.001). Myelitis was common in DN and AQP4-IgG+, while optic neuritis in MOG-IgG+. Relapse rates were highest in AQP4-IgG+ (p < 0.001). Oligoclonal bands were more common in DN (39 %) than in AQP4-IgG+ (27.7 %) and MOG-IgG+ (25 %)(<em>p</em> < 0.0001). Area postrema lesions were more frequent in DN (<em>p</em> = 0.02). Rituximab was mainly used in AQP4-IgG+ and DN (<em>p</em> < 0.001), with lower failure in DN (4.8 % vs 18 %).</div></div><div><h3>Conclusion</h3><div>DN NMOSD shows distinct features but comparable disability to AQP4-IgG+ individuals. Conventional immunosuppressants seem effective, though further research is needed to clarify mechanisms and optimize treatment strategies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578822"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-12-11DOI: 10.1016/j.jneuroim.2025.578835
Qiong Long , Jiahui Xie , Zhenyu Yang , Bo Zhang , Jun Chen , Miao Tang , Xinyi Jiang , Fei Yang , Ewen Tu , Xuanqi Dong
Objective
Autoimmune encephalitis (AE), a prevalent neuroimmunological disorder, is primarily managed with immunotherapy. However, a subset of patients exhibits suboptimal responses to first-line treatments, and second-line options remain limited. This study investigates the efficacy and safety of a personalized ofatumumab (OFA) regimen guided by monitoring CD27 + CD19+ memory B cells in refractory AE.
Methods
We report three cases of anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis and one case of antibody-negative AE (NA-AE) refractory to corticosteroids and intravenous immunoglobulin (IVIG). OFA was initiated at 20 mg subcutaneously on days 0 and 7, with subsequent doses administered when peripheral blood CD27 + CD19+ memory B cells exceeded 0.05 % of peripheral blood mononuclear cells (PBMCs).
Results
After a median follow-up of 10 months (range: 6–12 months), all patients demonstrated clinical improvement, with significant reductions in modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores. One patient experienced relapse post-SARS-CoV-2 infection, while the remainder remained recurrence-free without drug-related adverse events.
Interpretation
CD27 + CD19+ memory B cell-guided OFA therapy may offer a novel strategy for refractory AE.
{"title":"Personalized Ofatumumab therapy for autoimmune encephalitis: A case series of four patients","authors":"Qiong Long , Jiahui Xie , Zhenyu Yang , Bo Zhang , Jun Chen , Miao Tang , Xinyi Jiang , Fei Yang , Ewen Tu , Xuanqi Dong","doi":"10.1016/j.jneuroim.2025.578835","DOIUrl":"10.1016/j.jneuroim.2025.578835","url":null,"abstract":"<div><h3>Objective</h3><div>Autoimmune encephalitis (AE), a prevalent neuroimmunological disorder, is primarily managed with immunotherapy. However, a subset of patients exhibits suboptimal responses to first-line treatments, and second-line options remain limited. This study investigates the efficacy and safety of a personalized ofatumumab (OFA) regimen guided by monitoring CD27 + CD19+ memory B cells in refractory AE.</div></div><div><h3>Methods</h3><div>We report three cases of anti-<em>N</em>-methyl-<span>d</span>-aspartate receptor (anti-NMDAR) encephalitis and one case of antibody-negative AE (NA-AE) refractory to corticosteroids and intravenous immunoglobulin (IVIG). OFA was initiated at 20 mg subcutaneously on days 0 and 7, with subsequent doses administered when peripheral blood CD27 + CD19+ memory B cells exceeded 0.05 % of peripheral blood mononuclear cells (PBMCs).</div></div><div><h3>Results</h3><div>After a median follow-up of 10 months (range: 6–12 months), all patients demonstrated clinical improvement, with significant reductions in modified Rankin Scale (mRS) and Clinical Assessment Scale in Autoimmune Encephalitis (CASE) scores. One patient experienced relapse post-SARS-CoV-2 infection, while the remainder remained recurrence-free without drug-related adverse events.</div></div><div><h3>Interpretation</h3><div>CD27 + CD19+ memory B cell-guided OFA therapy may offer a novel strategy for refractory AE.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578835"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145734291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-23DOI: 10.1016/j.jneuroim.2025.578817
Vinícius Boldrini , Edgar Carnero Contentti
According to the 2025 IPND consensus, live cell-based assays (live CBA) are now established as the reference standard for screening AQP4-IgG autoantibodies in patients suspected of having AQP4-IgG-positive Neuromyelitis optica spectrum (NMOSD). However, resource-limited settings in Latin America (LATAM), where even commercial kits (fixed CBA) can be scarce, face significant difficulties in accessing local live CBA due to its higher implementation cost, the time required for experimentation, and its technical complexity.
In this narrative review, we identified 85 published studies that provide evidence of CBA locally used in LATAM countries. We identified 18 studies (21.1%) that used “live CBA” as the exclusive AQP4-IgG testing method. Brazil was the only country that had participated in all these reports. Argentina (n = 2, 2.3%), Mexico (n = 1, 1.1%), and Colombia (n = 1, 1.1%) have participated in studies combining “live CBA and fixed CBA”. Our literature review suggests that live CBA availability is approximately 20% when considered as a single testing method, or up to 27.1% (n = 23) when used to varying degrees in conjunction with fixed CBA. Notably, several studies (n = 37, 43.5%) we analyzed relied solely on commercial fixed assays for AQP4-IgG testing. Worryingly, nearly one-third (n = 25, 29.4%) of the studies we analyzed still use commercial kits in combination with other non‑gold-standard methods to detect AQP4-IgG. In general, fixed CBA was the most sensitive method in 62 studies (72.9%) from LATAM.
Based on our findings, here, we critically discuss the pressing need for live CBA dissemination across LATAM countries. This initiative will lead to more accurate epidemiological data, enable faster diagnosis, and improve access to highly effective therapies for AQP4-IgG-positive NMOSD patients living in this part of the world.
{"title":"Limited availability of live CBA for AQP4-IgG testing and its consequences for the diagnosis and treatment of NMOSD in Latin American countries","authors":"Vinícius Boldrini , Edgar Carnero Contentti","doi":"10.1016/j.jneuroim.2025.578817","DOIUrl":"10.1016/j.jneuroim.2025.578817","url":null,"abstract":"<div><div>According to the 2025 IPND consensus, live cell-based assays (<em>live CBA</em>) are now established as the reference standard for screening AQP4-IgG autoantibodies in patients suspected of having AQP4-IgG-positive Neuromyelitis optica spectrum (NMOSD). However, resource-limited settings in Latin America (LATAM), where even commercial kits (<em>fixed CBA</em>) can be scarce, face significant difficulties in accessing local <em>live CBA</em> due to its higher implementation cost, the time required for experimentation, and its technical complexity.</div><div>In this narrative review, we identified 85 published studies that provide evidence of CBA locally used in LATAM countries. We identified 18 studies (21.1%) that used “<em>live CBA”</em> as the exclusive AQP4-IgG testing method. Brazil was the only country that had participated in all these reports. Argentina (<em>n</em> = 2, 2.3%), Mexico (<em>n</em> = 1, 1.1%), and Colombia (<em>n</em> = 1, 1.1%) have participated in studies combining “<em>live CBA and fixed CBA</em>”. Our literature review suggests that <em>live CBA</em> availability is approximately 20% when considered as a single testing method, or up to 27.1% (<em>n</em> = 23) when used to varying degrees in conjunction with <em>fixed CBA.</em> Notably, several studies (<em>n</em> = 37, 43.5%) we analyzed relied solely on commercial fixed assays for AQP4-IgG testing. Worryingly, nearly one-third (<em>n</em> = 25, 29.4%) of the studies we analyzed still use commercial kits in combination with other non‑gold-standard methods to detect AQP4-IgG. In general, <em>fixed CBA</em> was the most sensitive method in 62 studies (72.9%) from LATAM.</div><div>Based on our findings, here, we critically discuss the pressing need for <em>live CBA</em> dissemination across LATAM countries. This initiative will lead to more accurate epidemiological data, enable faster diagnosis, and improve access to highly effective therapies for AQP4-IgG-positive NMOSD patients living in this part of the world.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578817"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-01Epub Date: 2025-11-28DOI: 10.1016/j.jneuroim.2025.578824
Parth Aphale, Himanshu Shekhar, Shashank Dokania
{"title":"The need for functional correlation in assessing peripheral and CNS immunity during EBV reactivation","authors":"Parth Aphale, Himanshu Shekhar, Shashank Dokania","doi":"10.1016/j.jneuroim.2025.578824","DOIUrl":"10.1016/j.jneuroim.2025.578824","url":null,"abstract":"","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578824"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145683174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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