Journal of neuroimmunology最新文献

{"title":"Exploratory analysis of B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) across migraine phases","authors":"Nisha Smithi ,&nbsp;Pooja Singh ,&nbsp;Swathika Rajendran ,&nbsp;Harini Purushothaman ,&nbsp;Ameena Bee ,&nbsp;Vishnupriya Gurumoorthy Mani ,&nbsp;Sowmiya Mari ,&nbsp;Deepa Avadhani ,&nbsp;Rajesh Kumar Gandhirajan ,&nbsp;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}

{"title":"Characterizing double seronegative neuromyelitis optica spectrum disorder: A distinct subgroup or part of the continuum?","authors":"María Agustina Piedrabuena ,&nbsp;Mariano Marrodan ,&nbsp;María Agustina Zárate ,&nbsp;Marcela Fiol ,&nbsp;María Celica Ysrraelit ,&nbsp;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> &lt; 0.0001). DN had more relapses in the first two years (<em>p</em> = 0.02) and higher EDSS (<em>p</em> &lt; 0.001). Myelitis was common in DN and AQP4-IgG+, while optic neuritis in MOG-IgG+. Relapse rates were highest in AQP4-IgG+ (p &lt; 0.001). Oligoclonal bands were more common in DN (39 %) than in AQP4-IgG+ (27.7 %) and MOG-IgG+ (25 %)(<em>p</em> &lt; 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> &lt; 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}

{"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 ,&nbsp;Roberta Amoriello ,&nbsp;Olfa Maghrebi ,&nbsp;Chiara Ballerini ,&nbsp;Giovanni Baldi ,&nbsp;Roberta Arpino ,&nbsp;Marianna Abate ,&nbsp;Silvia Zappavigna ,&nbsp;Luisa Pastò ,&nbsp;Maria Pia Amato ,&nbsp;Michele Caraglia ,&nbsp;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}

{"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}

{"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 ,&nbsp;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}

{"title":"Personalized Ofatumumab therapy for autoimmune encephalitis: A case series of four patients","authors":"Qiong Long ,&nbsp;Jiahui Xie ,&nbsp;Zhenyu Yang ,&nbsp;Bo Zhang ,&nbsp;Jun Chen ,&nbsp;Miao Tang ,&nbsp;Xinyi Jiang ,&nbsp;Fei Yang ,&nbsp;Ewen Tu ,&nbsp;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}

{"title":"The need for functional correlation in assessing peripheral and CNS immunity during EBV reactivation","authors":"Parth Aphale,&nbsp;Himanshu Shekhar,&nbsp;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}

{"title":"Chlorogenic acid alleviates lipopolysaccharide-induced cognitive dysfunction through inhibiting CCR7-mediated neuroinflammation","authors":"Si-Si He ,&nbsp;Liang Liu ,&nbsp;Xiang-Qin Wang ,&nbsp;Han Wang ,&nbsp;Xuan-Qi Fu ,&nbsp;Ling-Xue Kong ,&nbsp;Si-Yi Wang ,&nbsp;Pu-Kai Wang ,&nbsp;Xia Cai ,&nbsp;Yong-Jian Wang","doi":"10.1016/j.jneuroim.2025.578826","DOIUrl":"10.1016/j.jneuroim.2025.578826","url":null,"abstract":"<div><div>Evidence indicates that C-Chemokine Receptor 7 (CCR7) is implicated in behavioral dysfunction and that chlorogenic acid (CGA) exerts beneficial effects on cognitive deficits. However, the precise mechanisms by which CCR7 regulates cognitive dysfunction and whether CGA exerts its therapeutic effects through modulation of CCR7 signaling remain to be elucidated. Here, we <strong>investigated the specific role</strong> and mechanism of CCR7 on LPS-induced cognitive deficits using wild type (WT) and CCR7 knockout (CCR7^−/−) mice, and assessed the protective effect of CGA against these deficits. We found <strong>intracerebroventricular (i.c.v.) injection of LPS</strong> in WT mice <strong>induced learning and behavioral deficits</strong> in the open field test and Morris water maze (MWM) task, which <strong>were ameliorated</strong> in LPS-treated CCR7^−/− mice. Furthermore, <strong>we observed increased expression of the anti-apoptotic marker Bcl-2 and synaptic markers (PSD95, SYN)</strong> in the hippocampus of LPS-treated CCR7^−/− mice compared to <strong>that in</strong> LPS-stimulated WT mice. One potential mechanism of this action was attributed to the inhibition of <strong>LPS-induced,</strong> CCR7-mediated astrocyte activation, which was accompanied by reduced activation of its downstream proinflammatory signaling pathways (NF-κB, p38 and JNK) and the decreased production of pro-inflammatory factors including COX-2, iNOS, TNF-α, IL-1β and IL-6 in the hippocampus of LPS-treated CCR7^−/− mice. Importantly, we demonstrated CGA <strong>ameliorated</strong> LPS-induced cognitive dysfunction, at least in part, through inhibition of CCR7-mediated astrocyte activation and its downstream NF-κB, p38 and JNK pathway activation. Collectively, precise elucidation of the inhibitory effect of CGA on CCR7 signaling in LPS-stimulated mice contributes to the development of strategies for controlling neuroinflammation-mediated cognitive disorders.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"411 ","pages":"Article 578826"},"PeriodicalIF":2.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145668811","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}

{"title":"Ursolic acid enhances social behavior and modulates Th1, Th17, and T regulatory cell-related transcription factor signaling in the BTBR T+ Itpr3tf/J mouse model of autism","authors":"Thamer H. Albekairi,&nbsp;Abdulaziz S. Albakheet,&nbsp;Talal H. Alosaimi,&nbsp;Saleh A. Bakheet,&nbsp;Ahmed Nadeem,&nbsp;Sabry M. Attia,&nbsp;Mushtaq A. Ansari,&nbsp;Marwa H. Hussein,&nbsp;Mohamed A. Mahmoud,&nbsp;Sheikh F. Ahmad","doi":"10.1016/j.jneuroim.2025.578810","DOIUrl":"10.1016/j.jneuroim.2025.578810","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by unusual social interactions, limited speech, and repetitive behaviors or hobbies. The BTBR T⁺ Itpr3^tf/J (BTBR) inbred mice are commonly used as a model for ASD because they display many genetic traits associated with autism. Ursolic acid, a naturally occurring compound found in several plants, has shown promise as a treatment for various inflammatory disorders and related experimental models. This study aimed to explore the potential effects of ursolic acid on self-grooming, marble burying, and social behaviors in BTBR mice. We examined how ursolic acid affects the expression of Th1 (IFN-γ, TNF-α, STAT1, STAT4, and T-bet), Th17 (IL-17, RORγt, and STAT3), and T regulatory (Treg; IL-10, TGF-β1, and Foxp3) markers in CD4⁺ T cells within the spleens of BTBR and C57BL/6 mice. Additionally, we assessed the impact of ursolic acid on brain mRNA levels of IFN-γ, TNF-α, STAT1, STAT4, T-bet, IL-17, RORγ, STAT3, IL-10, TGF-β1, and Foxp3. Treatment with ursolic acid significantly affected behavioral issues in BTBR mice. In these animals, ursolic acid reduced the levels of Th1 and Th17 cells while increasing the levels of Treg cells. Furthermore, it decreased the expression of Th1 and Th17 mRNA and increased the expression of Treg-related mRNA in the brain. Our findings suggest that, due to its anti-inflammatory properties, ursolic acid may be a beneficial treatment for behavioral impairments in BTBR mice.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578810"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145569194","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}

{"title":"Early exposure of NOD/ShiLtJ mice to Freund's adjuvant prompts delayed, spontaneous progressive encephalomyelitis","authors":"Giuseppe Ranieri,&nbsp;Alberto Chiarugi,&nbsp;Daniela Buonvicino","doi":"10.1016/j.jneuroim.2025.578809","DOIUrl":"10.1016/j.jneuroim.2025.578809","url":null,"abstract":"<div><div>Drugs able to efficiently counteract primary progressive MS (PP-MS) remain an unmet need. The availability of reliable animal models of PP-MS might boost the identification of treatments capable of counteracting disease evolution. Recently, we characterized primary progressive EAE (PP-EAE) in NOD/ShiLtJ mice, showing that it recapitulates several key features of PPMS. However, a fundamental difference between PPMS and PPEAE is that the latter is triggered by loss of tolerance deliberately induced <em>via</em> peripheral expansion of myelin-specific effector T cells (Teff). In the present study, we report that NOD/ShiLtJ mice challenged with complete Freund's adjuvant (CFA) to prevent diabetes onset, developed spontaneous PP-EAE (SPP-EAE). Specifically, we report that the sole CFA challenge induced encephalomyelitis with a similar pattern of that prompted by the complete immunization protocol including CFA, pertussis toxin and MOG₃₅_–₅₅. Mice with SPP-EAE show primary progressive disease evolution, widespread neurodegeneration, and insensitivity to dexamethasone-dependent immunosuppression. Remarkably, however, at variance with the rapid onset of PP-EAE, SPP-EAE manifested after a latency of approximately 4.5 months following CFA injection. This model may represent a valuable experimental tool to study mechanisms underlying spontaneous loss of self-tolerance toward CNS antigens and MS progression, as well as to identify therapies of relevance to treatment of PMS patients.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"410 ","pages":"Article 578809"},"PeriodicalIF":2.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604693","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}