Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Rapidly Progressive and Relapsing Myelitis With Human T Lymphotropic Virus Type 1: A Case Report and Review of the Literature.","authors":"Andrew A Morrison, Rohini D Samudralwar, Joseph R Berger","doi":"10.1212/NXI.0000000000200570","DOIUrl":"10.1212/NXI.0000000000200570","url":null,"abstract":"<p><p>A patient presented to our center in the northeastern United States with recurrent longitudinally extensive myelitis which was ultimately attributed to infection with human T lymphotropic virus type 1 (HTLV-1). The most common neurologic presentation of this infection is an insidiously progressive myelopathy, although reports of rapid progression with acute onset have been described, including some associated with inflammatory changes on spinal cord MRI. Here, we describe a case of this rare entity and provide a review of the clinical, diagnostic, and treatment data of similar published cases. Along with our case, 44 published cases of rapidly progressive or relapsing HTLV-1-associated myelopathy (HAM) were identified and included in this review. Patients were predominantly female and from Japan, the Caribbean, or South America with a median time from clinical onset to presentation of 5 months. There were radiographic features of myelitis in 98% of patients, with 93% showing longitudinally extensive lesions and only 1 patient with normal spinal MRI. Most patients received steroid therapy and 94% of patients experienced symptomatic or radiographic improvement after treatment, although longitudinal follow-up of these patients was limited. In summary, HAM may present as a rapidly progressive or relapsing myelitis. Patients with acute myelitis should be tested for HTLV-1 infection, especially in cases of longitudinally extensive myelitis with relevant exposure risk factors and negative testing for alternate diagnoses. Although these patients often experience clinical and radiographic improvement with steroid therapy, further work is needed to clarify whether this treatment influences chronic disease progression.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200570"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13075422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147531424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CSF Proteins Associated With Neuroaxonal Damage in Early Active Multiple Sclerosis.","authors":"Felix Luessi, Chiara Starvaggi Cucuzza, Sinah Engel, Arda Civelek, Falk Steffen, Thomas Koeck, Philipp S Wild, Ingrid Kockum, Tomas Olsson, Stefan Bittner, Fredrik Piehl, Frauke Zipp","doi":"10.1212/NXI.0000000000200564","DOIUrl":"10.1212/NXI.0000000000200564","url":null,"abstract":"<p><strong>Background and objectives: </strong>The aim of this study was to identify biological processes associated with neuroaxonal degeneration in multiple sclerosis (MS) by analyzing protein patterns linked to neurofilament light (NfL) protein in CSF and serum samples.</p><p><strong>Methods: </strong>The highly sensitive proximity extension assay technology was used to quantify protein levels in paired CSF and serum samples from treatment-naïve, early-stage active MS patients (n = 114). The cohort was stratified into above and below median of CSF-NfL level. A discovery phase identified proteins upregulated in CSF, and a validation cohort (n = 128) confirmed findings in a more clinically diverse MS population, including patients receiving disease-modifying therapies.</p><p><strong>Results: </strong>In the discovery cohort, 13 proteins were upregulated in CSF (leukocyte immunoglobulin like receptor B4, CXCL6, CXCL5, cluster of differentiation 38, CCL19, CXCL11, IMPA1, macrophage scavenger receptor 1 (MSR1), CXCL10, monocyte chemotactic protein 2, ITM2A, TNFRSF12A, and CCL23). It is important to note that associations with CCL19, CXCL11, MSR1, CXCL10, TNFRSF12A, and CCL23 were replicated in a validation MS cohort. By contrast, no consistent serum protein profiles associated with serum levels of NfL could be discerned in this group-based analysis. Furthermore, 75 CSF proteins showed a positive adjusted linear association with CSF-NfL, whereas no such significant association remained in the corresponding analysis in serum.</p><p><strong>Discussion: </strong>The identified and replicated CSF protein profile indicates distinct inflammatory processes associated with ongoing neuroaxonal degeneration. All of these most robust 6 proinflammatory markers-CCL19, CXCL11, MSR1, CXCL10, TNFRSF12A, and CCL23-independently replicated and were individually observed to be relevant in the context of MS. These findings may further elucidate the immunologic pathways underlying disease processes leading to neuroaxonal degeneration.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200564"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HLA Associations Differ by Ethnicity and Aquaporin-4 Antibody Status in Patients With Neuromyelitis Optica Spectrum Disorders.","authors":"Moritz Niederschweiberer, Georgia Panagiotaropoulou, Marcelo A Fernandez-Viña, Gonzalo Montero-Martin, Kazutoyo Osoegawa, Megan Behne, Andre Franke, Wolfgang Lieb, Sven Jarius, Brigitte Wildemann, Patrick Schindler, Carolin Otto, Friedemann Paul, Eoin P Flanagan, Lawrence J Cook, Jorge Oksenberg, Michael R Yeaman, Stephan Ripke, Klemens Ruprecht","doi":"10.1212/NXI.0000000000200562","DOIUrl":"10.1212/NXI.0000000000200562","url":null,"abstract":"<p><strong>Background and objectives: </strong>Neuromyelitis optica spectrum disorders (NMOSDs) comprise inflammatory processes of the CNS. Most patients with NMOSD have serum immunoglobulin (Ig) G autoantibodies directed against the astrocytic water channel aquaporin-4 (AQP4-IgG). In this study, we analyzed HLA allelic frequencies in a large cohort of patients with NMOSD, stratified by ethnicity and AQP4-IgG status, compared with healthy controls.</p><p><strong>Methods: </strong>Next-generation sequencing-based HLA class I and II genotyping was performed in 174 White, 45 Black, and 41 Hispanic AQP4-IgG-positive (AQP4-IgG+) patients with NMOSD; 49 White patients with AQP4-IgG-negative (AQP4-IgG-) NMOSD; and 2,427 White, 244 Black, and 155 Hispanic controls. Correction for multiple testing was performed using the Bonferroni method.</p><p><strong>Results: </strong>In White AQP4-IgG+ patients with NMOSD, the most significantly associated alleles were <i>HLA-DQA1*05:01:01</i> (30.1% vs 11.1%, odds ratio 3.43 [95% CI 2.65-4.42], corrected <i>p</i> = 8.95E-17), <i>HLA-DQB1*02:01:01</i> (29.9% vs 11.3%, 3.34 [2.58-4.31], corrected <i>p</i> = 4.33E-16), and <i>HLA-DRB1*03:01:01</i> (29.2% vs 11.6%, 3.15 [2.43-4.06], corrected <i>p</i> = 3.66E-14), followed by <i>HLA-B*08:01:01</i> (26% vs 10.4%, 3.02 [2.3-3.94] corrected <i>p</i> = 8.79E-12), <i>HLA-C*07:01:01</i> (27.8% vs 14%, 2.36 [1.81-3.04], corrected <i>p</i> = 2.44E-07), and <i>HLA-DRB3*01:01:02</i> (28% vs 14.7%, 2.27 [1.73-2.95], corrected <i>p</i> = 2.19E-06). The frequency of <i>HLA-DRB1*08:04:01</i> was higher in Black AQP4-IgG+ patients with NMOSD than in Black controls but did not achieve statistical significance (19.3% vs 5.7%, 3.92 [1.91-7.86], corrected <i>p</i> = 0.08). Nevertheless, when compared with a larger cohort of Black controls (n = 16,178), the frequency of <i>HLA-DRB1*08:04</i> (19.3% vs 5.1%, 4.46 [2.45-7.66], corrected <i>p</i> = 1.88E-03) was significantly higher in Black AQP4-IgG+ patients with NMOSD. No significant HLA associations were detected in AQP4-IgG+ Hispanic patients or White AQP4-IgG- patients with NMOSD.</p><p><strong>Discussion: </strong>This study confirms the previously recognized association of <i>HLA-DRB1*03:01</i> with AQP4-IgG+ NMOSD in White patients and extends this association to the <i>HLA-DRB1*03:01:01</i>∼<i>HLA-DQA1*05:01:01</i>∼<i>HLA-DQB1*02:01:01</i> haplotype. Furthermore, it identifies an association of <i>HLA-DRB1*08:04</i> with AQP4-IgG+ NMOSD in Black patients. However, no HLA associations were detected in White AQP4-IgG- patients with NMOSD. The immunogenetic differences between AQP4-IgG+ and AQP4-IgG- NMOSD support pathophysiologic distinctions between these entities.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200562"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRUE-MOGAD Score: A Novel Scoring System to Identify MOGAD Among Positive MOG-IgG Test Results.","authors":"Andreu Vilaseca, Angeliki G Filippatou, Yana Said, Elia Sechi, Stephanie B Syc-Mazurek, Laura Cacciaguerra, Kai Guo, Nisa Vorasoot, Moritz Niederschweiberer, Smathorn Thakolwiboon, Jessica A Sagen, Sebastian A Lopez-Chiriboga, Jan-Mendelt Tillema, John J Chen, Sean J Pittock, Elias S Sotirchos, Eoin P Flanagan","doi":"10.1212/NXI.0000000000200563","DOIUrl":"10.1212/NXI.0000000000200563","url":null,"abstract":"<p><strong>Objectives: </strong>Myelin oligodendrocyte glycoprotein (MOG) antibodies (MOG-IgG) are a biomarker of MOG antibody-associated disease (MOGAD). However, false positives remain common. We aimed to develop a scoring tool to guide interpretation.</p><p><strong>Methods: </strong>Observational study of MOG-IgG-positive patients at Mayo Clinic (May 2022-December 2024). The primary outcome was fulfillment of 2023-MOGAD diagnostic criteria. Predictive variables were identified using logistic regression, and scoring systems were derived and evaluated using receiver operating characteristic analysis. Internal (n = 92) and external (Johns Hopkins, n = 117) validation was performed.</p><p><strong>Results: </strong>Of 215 MOG-IgG positive patients, 144 were true positive per 2023-MOGAD diagnostic criteria (positive predictive value, 67.0%). The <b>TRUE-</b><b>MOGAD</b> score included: <b>T</b>iters (MOG-IgG clear positive [+1 point]), <b>R</b>elapsing optic neuritis (≥3 [+1 point]), <b>U</b>nder 18 years at onset [+1 point], <b>E</b>ncephalitis phenotype (ADEM or cerebral cortical encephalitis at onset [+2 points]), <b>M</b>RI or other supportive features from 2023-MOGAD-criteria [+2 points], <b>O</b>ligoclonal bands in CSF [-2 points], <b>G</b>radually progressive or <b>A</b>brupt onset [-2 points], and <b>D</b>isappearance ≥1 T2-lesion [+1 point]. The score showed an area under the curve (AUC) of 0.983 (95%CI 0.961-1.000). The score was validated internally (AUC = 0.976) and externally (AUC = 0.977).</p><p><strong>Discussion: </strong>The TRUE-MOGAD score is a practical tool that accurately identifies MOGAD among positive MOG-IgG test results and may guide diagnostic and therapeutic decisions in clinical practice.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that a TRUE-MOGAD score of 2 or more accurately predicts MOGAD in patients with MOG-IgG titers of 1:20 or higher using the assay described.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200563"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13045729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low Prevalence and Inconsistency of LRP4-IgG Detection in Suspected Myasthenia Gravis: A Multicenter CBA Comparison.","authors":"Ilaria Gligora, Pietro Businaro, Lucrezia Serra, Silvia De Pasqua, Fortuna Ricciardiello, Luana Morelli, Chiara Morandi, Stefano Masciocchi, Antonio Malvaso, Corrado Ballestracci, Vitantonio Di Stasi, Veria Vacchiano, Anna Fetta, Simone Rossi, Keivan Kaveh Moghadam, Giovanni Rizzo, Domenica Chiara Milano, Andrea Zini, Duccio Maria Cordelli, Rita Rinaldi, Vincenzo Donadio, Rocco Liguori, Matteo Gastaldi, Maria Pia Giannoccaro","doi":"10.1212/NXI.0000000000200554","DOIUrl":"10.1212/NXI.0000000000200554","url":null,"abstract":"<p><strong>Background and objectives: </strong>Myasthenia gravis (MG) is an autoimmune disorder primarily caused by antibodies targeting neuromuscular junction proteins, particularly the acetylcholine receptor and the muscle-specific tyrosine kinase. However, 10%-20% of patients with MG are double-seronegative (dsMG). Antibodies against low-density lipoprotein receptor-related protein 4 (LRP4-IgG) have been found in a variable proportion of dsMG cases, but their frequency and clinical relevance remain unclear because of differences in assay methodologies and study populations. In this study, we assessed the frequency of LRP4-IgG in patients with suspected MG using different cell-based assay (CBA) protocols.</p><p><strong>Methods: </strong>In this multicenter observational study, we enrolled consecutive patients presenting with symptoms suggestive of MG. LRP4-IgG was tested by 2 centers using 3 different CBAs: live (l-CBA), methanol-fixed (mf-CBA), and paraformaldehyde-fixed (pf-CBA). Patients were classified as having MG or other disorders (ODs). Positive samples were cross-tested between centers.</p><p><strong>Results: </strong>Among 684 patients (302 with MG, 382 with ODs), LRP4-IgG was detected by mf-CBA in 2% (6/302) of MG cases and in 0.52% (2/382) of OD cases. Among patients with MG, 3.9% (4/102) of dsMG and 1% (2/200) of seropositive patients tested positive. Only 50% of mf-CBA-positive cases were confirmed by pf-CBA, and none were detected by l-CBA. Cross-center testing showed partial reproducibility.</p><p><strong>Discussion: </strong>LRP4-IgG detection in suspected MG is rare and inconsistent across assays, suggesting that routine testing is not currently warranted and that these antibodies are at present of limited diagnostic value. These findings highlight the need for standardized, validated LRP4-IgG assays. Future studies should focus on direct comparison and harmonization of testing protocols to clarify the clinical utility of LRP4-IgG testing.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200554"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12931517/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146258870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Shared Epitope-Positive <i>HLA</i> Alleles Protect Against Alpha-Synuclein Pathology in a Model of Parkinson Disease.","authors":"Jonathan J Carver, Bryce A Pugh, Qin Ma, Stacy J Caillier, Rachael R Denbrock, Cindy C Martines, Alexandra E Puckett, Taylor C Roberson, Marcelo A Fernandez-Viña, Jill A Hollenbach, Jorge Oksenberg, Joseph Holoshitz, Alessandro Didonna","doi":"10.1212/NXI.0000000000200580","DOIUrl":"10.1212/NXI.0000000000200580","url":null,"abstract":"<p><strong>Background and objective: </strong>There is increasing evidence that human leukocyte antigen (<i>HLA</i>) allelic variants play a role in the genetic predisposition to Parkinson disease (PD). In this regard, we have recently reported that the <i>HLA-DRB1*04:01</i> allele, typified by residues Q/R-K/R-R-A-A at positions 70-74 in the HLA-DRβ1 chain in combination with valine at position 11 (11-V), confers moderate protective effects. In this study, we tested whether <i>HLA-DRB1*04:01</i> can modulate PD pathology in vivo.</p><p><strong>Methods: </strong>We induced the alpha-synuclein preformed fibrils seeding PD model in humanized mice expressing the <i>HLA-DRB1*04:01</i> or <i>HLA-DRB1*04:02</i> allele. We then performed a comprehensive histopathologic and molecular characterization of the main disease phenotypes by combining quantitative histopathology, RNA-sequencing, flow cytometry immunophenotyping, and cytokine profiling.</p><p><strong>Results: </strong>Mice expressing <i>HLA-DRB1*04:01</i> display limited alpha-synuclein aggregation and lower dopaminergic axonal injury compared with mice expressing <i>HLA-DRB1*04:02</i>, along with reduced systemic inflammation. We also show that the microglia compartment in <i>HLA-DRB1*04:01</i> mice is in an activated steady state, possibly suggesting their mechanistic involvement in alpha-synuclein clearance.</p><p><strong>Discussion: </strong>Altogether, our findings provide the first experimental evidence of the genetic association between the HLA locus and PD susceptibility and support a neuroprotective function for the <i>HLA-DRB1*04:01</i> allele against alpha-synuclein pathology.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200580"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13095347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytomegalovirus Drives the Development of Cytotoxic CD4⁺ T Cells in Patients With Multiple Sclerosis.","authors":"Cindy Hoeks, Bram Boeckx, Paulien Baeten, Doryssa Hermans, Joanna Randall, Bart Van Wijmeersch, Veronica Popescu, Veerle Somers, Piet Stinissen, Diether Lambrechts, Bieke Broux, Niels Hellings","doi":"10.1212/NXI.0000000000200561","DOIUrl":"10.1212/NXI.0000000000200561","url":null,"abstract":"<p><strong>Background and objectives: </strong>Chronic immune activation is a hallmark of latent viral infections and autoimmune disorders, profoundly shaping immune cell phenotypes, including CD4⁺ cytotoxic T lymphocytes (CD4 CTL). The mechanisms underlying CD4 CTL development remain elusive, although antigenic triggers and the local microenvironment are thought to influence their phenotype. In this study, it was investigated if CD4 CTL induced under different circumstances exhibit phenotypic differences.</p><p><strong>Methods: </strong>Using single cell multiomics, we analyzed CD4 CTL from healthy cytomegalovirus (CMV)-seropositive donors, patients with CMV-seronegative relapsing-remitting multiple sclerosis (RR-MS) (autoimmune trigger), and patients with CMV-seropositive RR-MS (combination of viral and autoimmune trigger).</p><p><strong>Results: </strong>Our findings reveal that the heterogeneous pool of CD4 CTL encompasses distinct subsets with divergent expression of proinflammatory, cytotoxic, and migratory markers. Moreover, we identified a pathogenic CD4 CTL subset coexpressing the MS-associated transcription factor eomesodermin (EOMES) and the migratory receptor class I-restricted T-cell-associated molecule, which accumulates in MS lesions and demonstrates resistance to natalizumab treatment.</p><p><strong>Discussion: </strong>CMV was implicated as a dominant driver of development of highly cytotoxic CD4⁺ T cells, as these cells were markedly enriched in CMV-seropositive individuals. This comprehensive phenotypic atlas of CD4 CTL advances our understanding of their development and highlights potential targets for diagnosing, treating, and preventing MS progression.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200561"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13010278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147504557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrin β1 Demarks Precursors of Brain-Residing Antibody-Secreting Cells in Multiple Sclerosis.","authors":"Kirsten L Kuiper, Laurens Bogers, Jasper Rip, Yifan van Hasselt, Marie-José Melief, Annet F Wierenga-Wolf, Romy A M Klein Kranenbarg, Eric Bindels, Harmen J G van de Werken, Janet de Beukelaar, Ide Smets, Beatrijs Wokke, Joost Smolders, Marvin M van Luijn","doi":"10.1212/NXI.0000000000200553","DOIUrl":"10.1212/NXI.0000000000200553","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is characterized by CXCR3⁺ memory B cells that infiltrate the CNS to mature into antibody-secreting cells (ASCs). It remains elusive how to benefit from this disease hallmark as a prognostic tool. We aimed to uncover markers that reflect B-cell entry and maturation in the CNS and, on that basis, explore associations with response to high-efficacy MS therapies.</p><p><strong>Methods: </strong>Ex vivo single-cell technologies were applied to blood samples and postmortem CNS suspensions from MS and control donors, either treated or untreated. In addition, in vitro assays were performed on blood samples from healthy individuals to functionally asses B-cell activation, differentiation, and transmigration.</p><p><strong>Results: </strong>Single-cell RNA sequencing revealed <i>ITGB1</i> (integrin β1/CD29) as a major discriminator of CXCR3⁺ memory B cells in blood, which was validated using spectral flow cytometry. CD29⁺CXCR3⁺ memory B cells preferentially crossed a brain microvascular endothelial layer and were highly receptive to T-cell help to become ASCs in vitro. In contrast to blood, CD29 and CXCR3 coexpression was restricted to ex vivo ASCs derived from CSF, meninges, and brain tissue of people with MS, which was supported by enhanced CD29 upregulation on in vitro-differentiated ASCs. While CD29 was downregulated on CXCR3⁺ memory B cells that accumulated in the blood of natalizumab-treated patients, CD29 levels were only reduced on CXCR3⁺ memory B cells that repopulated in cladribine-treated patients without early disease activity.</p><p><strong>Discussion: </strong>These findings put forward CD29 as a putative marker on CXCR3⁺ precursors of CNS-residing ASCs for predicting treatment responses in MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200553"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146207332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ganglion Cell Layer Compared With Inner Plexiform Layer Atrophy After Optic Neuritis Associated With NMOSD, MOGAD, and MS.","authors":"Angeliki G Filippatou, Georgios Gakis, Anna Bacchetti, Anna Kim, Yana Said, Brenna McCormack, Ting-Yi Lin, Adam Didouchevski, Nicole Pellegrini, Kathryn C Fitzgerald, Peter A Calabresi, Shiv Saidha, Elias S Sotirchos","doi":"10.1212/NXI.0000000000200567","DOIUrl":"10.1212/NXI.0000000000200567","url":null,"abstract":"<p><strong>Background and objectives: </strong>Optic neuritis (ON) is a common manifestation of multiple sclerosis (MS), aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder (AQP4+NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Compared with MS-ON, AQP4-ON and MOGAD-ON eyes exhibit more severe thinning of the macular composite ganglion cell + inner plexiform layer (GCIPL), as measured by optical coherence tomography (OCT). The individual measurement of the ganglion cell (GCL) and inner plexiform (IPL) layers, typically assessed together as the composite GCIPL thickness, has remained largely unexplored. In this study, we aimed to examine the relative contribution of GCL and IPL thinning to overall GCIPL thinning in MS-ON, AQP4-ON, and MOGAD-ON eyes.</p><p><strong>Methods: </strong>For the cross-sectional analysis, MS, AQP4+NMOSD, and MOGAD participants with a history of ON >6 months prior and healthy controls (HC) underwent retinal imaging. For the longitudinal analysis, the evolution of GCL and IPL thinning was examined in people with baseline OCT within 30 days of a first episode of acute ON.</p><p><strong>Results: </strong>In the cross-sectional cohort, GCL and IPL volumes were lower in AQP4-ON (n = 30 eyes) and MOGAD-ON (n = 47 eyes), as compared with MS-ON (n = 66 eyes), but did not differ between AQP4-ON and MOGAD-ON eyes. The GCL/GCIPL ratio was lower in ON eyes relative to HC and was correlated with GCIPL volume, with a similar pattern across disease groups. AQP4-ON and MOGAD-ON eyes had a lower GCL/GCIPL ratio compared with MS-ON, with no significant difference between AQP4-ON and MOGAD-ON. In the longitudinal cohort, the GCL/GCIPL ratio was already reduced in the ON eyes (n = 19 eyes) compared with the fellow non-ON eyes at the baseline scan within the first month from ON (-1.01% [-1.59% to -0.44%], <i>p</i> = 0.002). A greater loss of GCIPL volume after acute ON was associated with a greater decrease of the GCL/GCIPL ratio (r = 0.50, <i>p</i> < 0.001).</p><p><strong>Discussion: </strong>More severe GCIPL thinning after ON was associated with a lower GCL/GCIPL ratio, supporting that more GCL than IPL thinning occurs after ON. The pattern was similar across neuroinflammatory conditions including MS, MOGAD, and AQP4+NMOSD. Our findings may help shed light into dynamics of inner retinal layer atrophy after ON.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200567"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13020555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147513799","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-9 Regulates NF-kB-Mediated Activation of Astrocytes in Multiple Sclerosis Brain.","authors":"Miriam Cinotti, Susanna Amadio, Daniele Tidei, Gloria Donninelli, Costanza Stacchiotti, Veronica De Paolis, Emanuela Colombo, Anthea De Angelis, Francesca Ruffini, Gianvito Martino, Cinthia Farina, Chiara Parisi, Cinzia Volonté, Elisabetta Volpe","doi":"10.1212/NXI.0000000000200574","DOIUrl":"10.1212/NXI.0000000000200574","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"13 3","pages":"e200574"},"PeriodicalIF":8.0,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12959724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147348569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}