Journal of neuroimmunology最新文献

{"title":"N-type voltage-gated calcium channel antibody testing lacks diagnostic value in Lambert-Eaton myasthenic syndrome","authors":"Friederike A. Arlt ,&nbsp;Masoud Majed ,&nbsp;Jack Wu ,&nbsp;Anastasia Zekeridou ,&nbsp;Shahar Shelly ,&nbsp;Vanda A. Lennon ,&nbsp;Sean J. Pittock ,&nbsp;Andrew McKeon ,&nbsp;Christopher J. Klein ,&nbsp;Divyanshu Dubey ,&nbsp;John R. Mills","doi":"10.1016/j.jneuroim.2025.578681","DOIUrl":"10.1016/j.jneuroim.2025.578681","url":null,"abstract":"<div><h3>Introduction/aims</h3><div>Diagnostic evaluation for Lambert-Eaton myasthenic syndrome (LEMS) includes serological testing for voltage-gated calcium channel antibodies (VGCC-P/Q-type [VGCC-PQ] and VGCC-N-type [VGCC-N]). While VGCC-PQ antibodies are well-established biomarkers in LEMS, the clinical utility of VGCC-N antibody testing remains obscure. We aimed to determine the diagnostic value of VGCC-N antibody testing.</div></div><div><h3>Methods</h3><div>A retrospective cross-sectional study was performed. The Mayo Clinic electronic medical record from 1995 to 2021 was reviewed for inclusion of patients fitting clinical electrodiagnostic criteria for LEMS, who were evaluated for serum VGCC antibodies (<em>n</em> = 123). Available sera were additionally tested for SOX1 antibodies (<em>n</em> = 68). Healthy adults were tested for VGCC-PQ and VGCC-N antibodies (<em>n</em> = 122). Clinical performance of each antibody test was evaluated statistically.</div></div><div><h3>Results</h3><div>Among adult LEMS cases, 84.6 % (<em>n</em> = 99/117) tested positive for VGCC-PQ antibody while none of the healthy controls did. In contrast, 20.5 % (<em>n</em> = 24/117) were VGCC-N antibody positive, of which 95.8 % (<em>n</em> = 23/24) co-occurred with VGCC-PQ antibodies. The frequency of isolated VGCC-N antibody positivity was higher in controls than in LEMS (2.5 % [<em>n</em> = 3/122] vs. 0.9 % [<em>n</em> = 1/117]), and pediatric patients had no VGCC-N antibody reactivity. Neither VGCC-N antibody positivity nor titer was predictive of an associated small-cell lung cancer (SCLC-LEMS). By contrast, SOX1-IgG seropositivity associated significantly with SCLC-LEMS.</div></div><div><h3>Discussion</h3><div>Inclusion of VGCC-N antibody testing does not improve diagnostic accuracy for LEMS, nor does it serve as a predictor of LEMS-associated cancers in contrast to SOX1-IgG testing. We recommend the exclusion of VGCC-N antibody testing given its non-specific disease associations and poor positive predictive value in LEMS screening.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578681"},"PeriodicalIF":2.9,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144597495","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":"Association of plasma IL-33 levels with aggression in schizophrenia: A clinical study","authors":"Qi Zhang ,&nbsp;Li Li ,&nbsp;Zheng Gao ,&nbsp;Xue Li ,&nbsp;Peng Zhang ,&nbsp;Yujing Yang ,&nbsp;Caiyi Zhang","doi":"10.1016/j.jneuroim.2025.578680","DOIUrl":"10.1016/j.jneuroim.2025.578680","url":null,"abstract":"<div><div>Aggression in schizophrenia (SCZ) poses a serious risk to others and complicates treatment. Inflammation has been confirmed to be associated with aggression in SCZ, but specific biomarkers remain unidentified. This study aimed to measure plasma interleukin-33 (IL-33) levels and explore their association with aggression in SCZ for the first time. The enzyme-linked immunosorbent assay (ELISA) was used to measure the levels of IL-33 in SCZ with aggression (SCZ-Ag, <em>n</em> = 31) and non-aggression (NSCZ-Ag, <em>n</em> = 32), and healthy controls (HCs, <em>n</em> = 26). Aggression was measured using the Modified Overt Aggression Scale (MOAS), and clinical symptoms were assessed with the Positive and Negative Syndrome Scale (PANSS). The results showed that the plasma IL-33 levels were elevated in SCZ-Ag compared with NSCZ-Ag and HCs, with no significant difference between NSCZ-Ag and HCs. In the patient group, partial correlation analysis indicated a positive correlation between IL-33 levels and PANSS total scores, positive symptom subscores, and MOAS total scores. Regression analysis showed that a higher likelihood of aggression in SCZ was associated with elevated plasma IL-33 levels (OR = 1.075, 95 % <em>CI</em>: 1.023–1.129). ROC curve analysis showed that IL-33 (AUC = 0.713, 95 % <em>CI</em>: 0.582–0.844) demonstrated moderate performance in distinguishing SCZ-Ag from NSCZ-Ag. These findings suggest that elevated plasma IL-33 levels are a potential risk factor for aggression in patients with SCZ and are implicated in the clinical symptoms of patients. Increased plasma IL-33 levels may serve as a potential marker for aggression in SCZ. These findings require further validation in future studies.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578680"},"PeriodicalIF":2.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518080","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":"Network analysis of intrathecally synthesized proteins to unravel mechanisms of disease course in multiple sclerosis","authors":"Nora C. Welsh ,&nbsp;Krista D. DiSano ,&nbsp;Steven C. Pike,&nbsp;Michael Linzey ,&nbsp;Andrew D. Smith III,&nbsp;Andrew R. Pachner,&nbsp;Francesca Gilli","doi":"10.1016/j.jneuroim.2025.578678","DOIUrl":"10.1016/j.jneuroim.2025.578678","url":null,"abstract":"<div><div>Multiple sclerosis (MS) is a heterogeneous disease, in both clinical presentation and neuro-immunopathology. Proteins secreted into the cerebrospinal fluid (CSF) can serve as molecular proxies of these pathologies in the central nervous system (CNS) but are biased by leakage of serum proteins into the CSF. Thus, a detailed analysis of intrathecal protein production, i.e., the fraction of CSF protein synthesized locally within the CNS, rather than derived from passive transfer across the blood-CSF barrier, can provide valuable insights into the heterogenous immunological and neurodegenerative processes at play. To understand the dynamic biological processes involved in MS disease course mechanisms, we used network analysis to untangle the intricacies of intrathecally produced protein-to-protein relationships in 60 patients diagnosed with clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and primary progressive MS (PMS). These analyses revealed distinct immunological phenotypes linked to inflammation and neurodegeneration in the CNS in each disease course, providing novel insight into the disease course-specific pathophysiology of MS.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578678"},"PeriodicalIF":2.9,"publicationDate":"2025-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534902","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":"Paraneoplastic bilateral vocal cord paralysis in a patient with anti-Hu syndrome after receiving nivolumab: Case report and literature review","authors":"Seyda Erdoğan ,&nbsp;Elif Peker ,&nbsp;Ahmet Demirkazık ,&nbsp;Nursel Aydın ,&nbsp;Canan Yücesan","doi":"10.1016/j.jneuroim.2025.578679","DOIUrl":"10.1016/j.jneuroim.2025.578679","url":null,"abstract":"<div><div>Bilateral vocal cord paralysis (BVCP), a life-threatening condition often necessitating tracheotomy, has been infrequently reported as a paraneoplastic manifestation. We present the case of a 75-year-old male with small cell lung cancer who experienced distinct episodes of paraneoplastic neurological syndromes. The initial episode, occurring concomitant with the diagnosis of cancer and initiation of chemotherapy, was characterized by epileptic seizures and ataxia, which resolved following treatment with immunotherapy. The subsequent episode, presenting as BVCP, developed after the fourth dose of nivolumab as part of the patient's paraneoplastic syndrome. Brain magnetic resonance imaging revealed bilateral hyperintense lesions in the anterior medulla oblongata on T2/FLAIR-weighted sequences. To the best of our knowledge, this represents the first documented case of paraneoplastic BVCP associated with bilateral bulbar lesions, potentially triggered by immune checkpoint inhibitor therapy.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578679"},"PeriodicalIF":2.9,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534904","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":"MiR-223-3p promote microglia “M2” polarization by targeting FOXO3a in subarachnoid hemorrhage","authors":"Xiaolong Yao ,&nbsp;Bizhou Bie ,&nbsp;Zhizhong Wang ,&nbsp;Yingchun Chen ,&nbsp;Liuqing Sheng ,&nbsp;Mingchang Li","doi":"10.1016/j.jneuroim.2025.578677","DOIUrl":"10.1016/j.jneuroim.2025.578677","url":null,"abstract":"<div><h3>Objective</h3><div>Exosome-derived micorRNAs (miRs) play important role in regulation the inflammatory response in subarachnoid hemorrhage (SAH). However, the ability of miR-223-3p, which is enriched in astrocyte-derived exosomes, to regulate FOXO3a in microglia is still unclear.</div></div><div><h3>Methods</h3><div>MiR-223-3p in CSF from SAH patients was measured by qRT–PCR. Rats and BV2 cells were used to establish SAH model. Neurological function was evaluated by the mNSS, rotarod test, and Morris water maze. QRT–PCR and enzyme-linked immunosorbent assay (ELISA) were used to analyze oxidative stress and inflammatory factors interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNF-α). The levels of FOXO3a, TLR4, NLRP3, NF-κB, iNOS, Cox2, Nrf2 and HO-1 were detected by WB. The exosomes were labeled with KPH67, and uptaken by microglia, detecting by IF.</div></div><div><h3>Results</h3><div>Among the miRs involved in SAH, miR-223-3p exhibited one of the greatest change. MiR-223-3p in the brain tissue of SAH rats was upregulated. Moreover, the upregulation of miR-223-3p significantly improved neurological deficits and reduced brain edema. Meanwhile, miR-223-3p reduced the inflammatory factors like IL-1β, IL-6, TNF-α, and decreased oxidative stress, inhibited the activation of NF-κB, TLR4/NLRP3 in microglia by targeting Foxo3a. The “M1” polarization marker, including iNOS, Cox2, TLR4, NLRP3 and NF-κB, in microglia decreased markedly after the overexpression of miR-223-3p. Moreover, miR-223-3p targets FOXO3a and inhibits it expression no matter <em>in vitro</em> or <em>in vivo</em>. <em>In vitro</em>, both miR-223-3p mimics and astrocyte-derived exosomes obviously increased the expression of miR-223-3p in microglia.</div></div><div><h3>Conclusion</h3><div>In SAH, astrocyte-derived exosomes rich in miR-223-3p may regulate the activation and phenotype of microglia by targeting FOXO3a, resulting in the inhibition of inflammatory injury.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578677"},"PeriodicalIF":2.9,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144534903","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":"Exploring the effectiveness of cytarabine in people living with HIV with progressive multifocal leukoencephalopathy: a retrospective cohort study in Chongqing, China","authors":"Min Liu ,&nbsp;Huan Li ,&nbsp;Mei Li,&nbsp;Qin Zeng,&nbsp;Hong-Hong Yang","doi":"10.1016/j.jneuroim.2025.578676","DOIUrl":"10.1016/j.jneuroim.2025.578676","url":null,"abstract":"<div><h3>Background</h3><div>The incidence of progressive multifocal leukoencephalopathy (PML) in people living with HIV (PLWH) is approximately 2 %–4 % globally, and there is currently no effective therapeutic strategy. Cytarabine has been reported to increase the survival probability of PLWH with PML; however, its effectiveness remains controversial. The present study aimed to explore whether cytarabine improves the outcomes of PLWH with PML.</div></div><div><h3>Methods</h3><div>We retrospectively collected data from PLWH who were admitted to the hospital and were diagnosed with PML from January 1, 2019, to October 31, 2023, in Chongqing, China, and then stratified the patients into two groups according to whether they did or did not receive cytarabine treatment. The clinical outcomes and mortality rates were assessed.</div></div><div><h3>Results</h3><div>A total of 41 patients were included in our study. The median age at the time of hospital admission was 44 years [interquartile range (IQR), 36–51]. The patient cohort had a median CD4+ T-cell count of 68.0 (38.5–109.5) cells/mL and a median HIV viral load of 5.05 (2.53, 5.76) log10 copies/ml. 15 patients received intravenous cytarabine and antiretroviral therapy (ART), and 26 patients did not receive cytarabine (24 patients received ART, and 2 patients did not receive ART). In the cytarabine group, 7 patients (46.7 %) died, 4 patients (26.7 %) improved, 2 patients (13.3 %) stabilized, and 2 patients (13.3 %) worsened. In the noncytarabine group, 15 (57.7 %) patients died, 7 patients (26.9 %) improved, 3 patients (11.5 %) stabilized, and 1 patient (3.9 %) worsened; the clinical outcomes did not significantly differ between the two groups (<em>P</em> &gt; 0.05). The overall mortality rate and 30-day, 90-day, 180-day and one-year mortality rates were lower in the cytarabine group than in the noncytarabine group, but the differences were not significant (<em>P</em> &gt; 0.05).</div></div><div><h3>Conclusions</h3><div>Our results suggest that treatment with cytarabine seems to fail to improve the survival rates of PLWH with PML. Our study is small and cannot definitively rule out cytarabine activity against PML. Future studies in a larger cohort and longer observations are needed.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578676"},"PeriodicalIF":2.9,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144518111","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":"Evolution and significance of neuronal surface autoantibodies after Japanese encephalitis","authors":"Anjan Nibber ,&nbsp;Bridget Wills ,&nbsp;Philippa Pettingill ,&nbsp;Hannah Fox ,&nbsp;Tran Thi Nhu Thuy ,&nbsp;Nguyen Van Vinh Chau ,&nbsp;Patrick Waters ,&nbsp;Rachel Kneen ,&nbsp;Yael Hacohen ,&nbsp;Christopher E. Uy ,&nbsp;Sayaphet Rattanavong ,&nbsp;Mayfong Mayxay ,&nbsp;Audrey Dubot-Pérès ,&nbsp;Manivanh Vongsouvath ,&nbsp;Viengmon Davong ,&nbsp;Vilada Chansamouth ,&nbsp;Koukeo Phommasone ,&nbsp;Bethan Lang ,&nbsp;Paul N. Newton ,&nbsp;Tom Solomon ,&nbsp;Sarosh R. Irani","doi":"10.1016/j.jneuroim.2025.578671","DOIUrl":"10.1016/j.jneuroim.2025.578671","url":null,"abstract":"<div><div>NMDAR-antibody encephalitis can arise as a post-infectious ‘relapse’ following HSV encephalitis. We asked whether a similar condition might occur after Japanese Encephalitis (JE). Cell-based assays for antigen-specific antibodies and IgG binding to the surface of live hippocampal neurons were performed on 13 CSFs and 65 sera, many sampled longitudinally, from 34 Vietnamese children with JE. Three month outcomes were scored according to a pediatric post-encephalitis scale; clinical features focussed on new onset symptoms during the follow-up, blinded to antibody results. Ten/34 children (29 %) had serum antibodies against known neuronal-surface antigens, 4 NMDAR, 4 CASPR2, 1 GABAAR and 1 LGI1, detected from day 23 after onset. In addition, 8/10 (80 %) of these children and 13/24 (54 %) others had antibodies that bound in a distinctive pattern to live hippocampal neurons (HN-Abs), four detected on days 9–12. A relapse was only considered possible in 5 patients, two with specific neuronal surface antibodies (NSAbs). Neither specific NSAbs (<em>p</em> = 1.00) nor HN-Abs (p = 1.00).were more common in patients with possible relapse than in those with unlikely relapse. There was a modest trend towards worse outcome scores in patients with known NSAbs than in the remaining patients (<em>p</em> = 0.089). Antibodies to neuronal surface proteins, known and unknown, are common in children after JE. Caution is urged in defining post-infectious autoimmune encephalitis on the basis of a positive neuronal antibody and new onset symptoms or deterioration following recovery from JE, or in initiating immunotherapy without confirmatory evidence of a time-dependent encephalitic illness defined by published guidelines.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578671"},"PeriodicalIF":2.9,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144524337","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":"Gene prediction link between metabolite-mediated inflammatory factors and vertigo","authors":"Moyan Wang ,&nbsp;Qi Han ,&nbsp;Xin Teng ,&nbsp;Ke Xiang ,&nbsp;Li Sun","doi":"10.1016/j.jneuroim.2025.578675","DOIUrl":"10.1016/j.jneuroim.2025.578675","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the causal relationship between inflammatory factors and vertigo diseases, and to determine and quantify the role of 1400 metabolites as potential mediators.</div></div><div><h3>Methods</h3><div>Using the summary data of the whole genome association study(genome-wide association study, GWAS), two-sample Mendel randomization(Mendelian randomization, MR)analysis was performed on four vertigo diseases and 1400 inflammatory factors predicted by genes.Furthermore, we used two-step MR to quantify the effects of 1400 metabolite-mediated inflammatory factors on vertigo.</div></div><div><h3>Results</h3><div>MR analysis identified higher genes predicted inflammatory factors to increase the risk of vertigo. Reverse studies of inflammatory factors on vertigo have shown that gene-predicted vertigo has no effect on most of the selected inflammatory factors. Metabolites-mediated gene predictions are more associated with inflammatory factors, and mediating effects lack strong evidence support.</div></div><div><h3>Conclusion</h3><div>In summary, our study identified a causal relationship between inflammatory factors and vertigo, where the proportion of effects mediated by blood metabolites and other metabolites is small, but the majority of the effects of inflammatory factors on vertigo remain unclear. Additional risk factors as potential mediating factors require further research. In clinical practice, blood test indicators for patients with vertigo deserve in-depth exploration.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578675"},"PeriodicalIF":2.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144501919","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":"Occult cartilaginous choristoma in a child with myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis","authors":"Sayaka Enomoto ,&nbsp;Hiroki Tsuchiya ,&nbsp;Yoshiyuki Ayada ,&nbsp;Yoshiki Takai ,&nbsp;Toshiki Takenouchi","doi":"10.1016/j.jneuroim.2025.578674","DOIUrl":"10.1016/j.jneuroim.2025.578674","url":null,"abstract":"<div><div>Myelin oligodendrocyte glycoprotein antibody-associated disease is a central inflammatory demyelinating disorder that cause diverse neurological symptoms. Paraneoplastic neurologic syndromes occur in association with malignant neoplasms and manifest with a wide range of neuropsychiatric symptoms. Paraneoplastic neurological syndrome is rare in myelin oligodendrocyte glycoprotein antibody-associated disease and, when reported, is typically seen in adults. Herein, we report a 3-year-old girl who presented with lower limb paralysis, urinary retention, and seropositivity for myelin oligodendrocyte glycoprotein antibody. Her symptoms did not respond to various immunotherapies. She was incidentally found to have a cartilaginous choristoma in the neck, after surgical resection of which, she showed symptomatic recovery without recurrence. Immunohistochemical analysis of the resected tumor revealed expression of myelin oligodendrocyte glycoprotein within the cartilage tissue. Based on this case experience, children presenting with myelin oligodendrocyte glycoprotein antibody-associated disease who fail to respond to immunotherapies may need prompt screening for occult tumors.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578674"},"PeriodicalIF":2.9,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365253","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":"Therapeutic potential of S-nitrosoglutathione reductase inhibitor in B cell-driven experimental autoimmune encephalomyelitis","authors":"Jeseong Won ,&nbsp;Judong Kim ,&nbsp;Fei Qiao ,&nbsp;Avtar K. Singh ,&nbsp;Inderjit Singh","doi":"10.1016/j.jneuroim.2025.578673","DOIUrl":"10.1016/j.jneuroim.2025.578673","url":null,"abstract":"<div><div>We previously reported that S-nitrosoglutathione (GSNO) and GSNO reductase inhibitors, which increase endogenous GSNO, mitigate T cell-dependent experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, by suppressing Th1 and Th17 effector T cells while promoting regulatory T cells (Tregs). In this study, we demonstrate that the GSNO reductase inhibitor (N6022) also alleviates B cell-dependent EAE in C57BL/6 mice immunized with recombinant human myelin oligodendrocyte glycoprotein (rhMOG₁_–₁₂₅). Daily N6022 treatment following disease onset significantly reduced clinical EAE disease symptoms. N6022 treatment increased the number of CD1d^hiCD5⁺ regulatory B cells (Bregs) in the spleen and inhibited B cell expression of the effector cytokine IL-6 while enhancing their expression of the regulatory cytokine IL-10. Accordingly, N6022 reduced the number of pathogenic effector CD4⁺ T cells (Th1 and Th17) in the spleen and decreased the expressions of proinflammatory cytokines associated with these T cells (IFN-γ and IL-17a), and increased the number of Treg cells with increased serum levels of IL-10. N6022 treatment also suppressed B cell maturation into plasma cells, lowering serum autoantibody levels against human MOG₁_–₁₂₅ IgG. Similar observations were made in the spinal cord, where N6022 treatment modulated B cell expression of regulatory versus effector cytokines (IL-10 &gt; IL-6) and the expansion of regulatory versus effector T cells (Treg &gt; Th1/Th17). These findings document that GSNOR inhibitors may potentially serve as effective immunomodulators in both T cell- and B cell-mediated EAE and multiple sclerosis.</div></div>","PeriodicalId":16671,"journal":{"name":"Journal of neuroimmunology","volume":"406 ","pages":"Article 578673"},"PeriodicalIF":2.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144471361","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}