Neurology® Neuroimmunology & Neuroinflammation最新文献

{"title":"Small Nuclear Ribonucleoprotein Autoantibody Associated With Blood-Nerve Barrier Breakdown in Guillain-Barré Syndrome.","authors":"Fumitaka Shimizu, Michiaki Koga, Yoichi Mizukami, Kenji Watanabe, Ryota Sato, Yukio Takeshita, Toshihiko Maeda, Takashi Kanda, Masayuki Nakamori","doi":"10.1212/NXI.0000000000200405","DOIUrl":"10.1212/NXI.0000000000200405","url":null,"abstract":"<p><strong>Background and objectives: </strong>Breakdown of the blood-nerve barrier (BNB) is observed in patients with Guillain-Barré syndrome (GBS); however, the molecular mechanism underlying this phenomenon remains unclear.The aim of this study was to identify antibodies against the BNB-endothelial cells that initiate BNB breakdown in patients with GBS.</p><p><strong>Methods: </strong>We purified IgGs from the serum samples of patients with GBS (n = 77) during the acute phase, disease controls ([DCs], n = 51), and healthy controls ([HCs], n = 24). Human peripheral nerve microvascular endothelial cells (PnMECs) were incubated with IgG. Molecular changes in PnMECs after GBS-IgG exposure were evaluated using RNA-seq and a high-content imaging system. U1-small nuclear ribonucleoprotein (U1-snRNP) autoantibodies were detected using an ELISA. The clinical information of U1-snRNP antibody-positive GBS patients was verified.</p><p><strong>Results: </strong>GBS-IgGs significantly increased NF-κB nuclear translocation and permeability of the 10-kDa dextran in PnMECs compared with DC-IgGs or HC-IgGs. RNA-seq analyses of PnMECs demonstrated that NF-κB p65 in the center of the network analysis, snRNPs as upstream genes of NF-κB p65, and CXCR5 as downstream genes of NF-κB p65 were important molecules after GBS-IgG exposure. The protein level of claudin-5 and U1-snRNP was significantly reduced while that of CXCR5 was significantly increased after incubation with IgG from patients with GBS, compared with that from HCs. The rate of U1-snRNP antibody positivity was 36% (28 of 77) in patients with GBS, 7% (2 of 28) in DCs, and 0% (0 of 16) in HCs. The serum titer of snRNP antibody decreased after treatment. Both cerebral spinal fluid protein and albumin quotient (QALB)/QALBLIM were higher in snRNP antibody-positive GBS patients than in snRNP antibody-negative GBS patients. IgG from U1-snRNP antibody-positive GBS patients decreased the barrier function and claudin-5 expression more than that from HCs in an in vitro BNB coculture model. The reduction in U1-snRNP antibody decreased the biological effect of IgG from GBS patients with U1-snRNP antibody on the increased permeability of PnMECs.</p><p><strong>Discussion: </strong>U1-snRNP autoantibodies are associated with the breakdown of BNB in GBS, through the reduction of U1-snRNP and claudin-5 and the induction of NF-κB activation in BNB-endothelial cells. A temporary autoantibody response against snRNP may be boosted by the periodic response to infection in GBS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200405"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12092546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144102337","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":"Relapses in Anti-NMDAR Encephalitis: Clinical Characterization and Predictive Features.","authors":"Nicolás Lundahl Ciano-Petersen, Macarena Villagrán-García, Sergio Muñiz-Castrillo, Antonio Farina, Alberto Vogrig, David Goncalves, Fabien Nicole, Véronique Rogemond, Geraldine Picard, Mélodie Aubart, Dimitri Psimaras, Begoña Oliver, Pedro J Serrano-Castro, Bastien Joubert, Jerome Honnorat","doi":"10.1212/NXI.0000000000200421","DOIUrl":"10.1212/NXI.0000000000200421","url":null,"abstract":"<p><strong>Background and objectives: </strong>During the recovery phase of anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, up to 25% of relapses have been reported. Herein, we aimed to clinically characterize these relapses, analyze potential clinical predictors during the first episode, and evaluate the impact of immunotherapy in their occurrence.</p><p><strong>Methods: </strong>This was a retrospective observational study of patients diagnosed with anti-NMDAR encephalitis relapses between January 2007 and June 2022 at the French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis with a follow-up longer than 1 year.</p><p><strong>Results: </strong>Among 507 patients, 49 (9%) presented relapses after a median time of 720 days (range 149-8,280) and a median follow-up of 1752 days (range 390-9,229 days, interquartile range 1760 days). A total of 36 patients (73%) experienced 1 relapse, 9 (18%) had 2, and 4 (8%) had 3 relapses. Most patients presented an isolated core symptom (25/45, 55%). Relapses were less severe than the first episode, as reflected by a lower maximal modified Rankin Scale (median 5, range 3-5, vs median 3, range 0-6; <i>p</i> = 0.0001). At the first episode, patients experiencing relapses had shorter intensive care unit stays (22 days; vs 39 days; <i>p</i> = 0.04). In addition, presenting CSF pleocytosis >20 white blood cell decreased the risk of relapse by 71% (HR 0.29; CI 0.13-0.66; <i>p</i> = 0.003), and having a paraneoplastic etiology decreased the risk by 68% (HR 0.32; CI 0.12-0.87; <i>p</i> = 0.02). Moreover, during the first episode, they were treated less frequently with first-line (39/49, 79%, vs 190/197, 96%; <i>p</i> = 0.0001) and second-line immunotherapies (20/49, 40%, vs 142/197, 72%; <i>p</i> = 0.0001) and more frequently with delay >30 days (20/38, 52%, vs 58/185, 31%; <i>p</i> = 0.01) and >60 days (10/20, 50%, vs 39/138, 28%; <i>p</i> = 0.04), respectively. In addition, administering rituximab during the first episode with a delay <60 days decreased the risk of relapse by 60% (HR 0.40; CI 0.19-0.84; <i>p</i> = 0.01).</p><p><strong>Discussion: </strong>Relapses of anti-NMDAR encephalitis are uncommon, mostly monosymptomatic, and less severe than the first episode. At onset, presenting CSF pleocytosis or an underlying tumor decreases the risk of relapses. In addition, the early administration of first-line and second-line immunotherapies, particularly rituximab, could protect against further relapses.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 4","pages":"e200421"},"PeriodicalIF":7.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326454","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":"Chronic Dengue Virus Encephalitis: A Case Study and Metagenomic Analysis.","authors":"Gabriela Abrahao Allioni, Gabriel Samir Martins de Souza, Julia Haddad Labello, Gabriel Saboia De Araújo Torres, Daniel Lacerda da Costa, Yuri R Casal, Amaro Nunes Duarte-Neto, Erick Gustavo Dorlass, Deyvid Amgarten, Fernanda de Mello Malta, André Mário Doi, Gustavo Bruniera Peres Fernandes, Joao Renato Rebello Pinho, Germana Titoneli Vieira, Luiz H Castro, Bruno Fukelmann Guedes","doi":"10.1212/NXI.0000000000200394","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200394","url":null,"abstract":"<p><strong>Background and objectives: </strong>Dengue virus (DENV) infection can cause acute encephalitis. Chronic encephalitis with progressive dementia is rarely reported.</p><p><strong>Methods: </strong>We present a case of chronic encephalitis with rapidly progressive dementia, in which a potential DENV brain infection was identified with brain tissue metagenomic next-generation sequencing. Brain pathology and molecular diagnosis are also presented.</p><p><strong>Results: </strong>A 20-year-old man from SP, Brazil, presented with rapidly progressive dementia, speech apraxia, and apathy in June 2022. By January 2023, cognitive testing showed severe global impairment (MMSE score of 18/30). MRI revealed white matter abnormalities and atrophy; CSF analysis disclosed a mild lymphocytic pleocytosis, mildly elevated protein levels, and positive CSF oligoclonal bands. Despite extensive testing ruling out common infectious and inflammatory causes, the patient's condition worsened with executive dysfunction, language impairment, tremors, and myoclonus. In August 2023, a brain biopsy and next-generation sequencing identified DENV-1 genotype V, linked to Brazilian sequences from 2000 to 2022.</p><p><strong>Discussion: </strong>This case highlights a challenging instance of encephalitis with unknown etiology, where metagenomic analysis detected DENV-1 RNA in brain tissue, suggesting a possible cause.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 3","pages":"e200394"},"PeriodicalIF":7.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023406","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":"Evolution of Chronic Lesion Tissue in Relapsing-Remitting Patients With Multiple Sclerosis: An Association With Disease Progression.","authors":"Samuel Klistorner, Michael Barnett, John D E Parratt, Con Yiannikas, Chenyu Wang, Dongang Wang, Andy Shieh, Alexander Klistorner","doi":"10.1212/NXI.0000000000200377","DOIUrl":"10.1212/NXI.0000000000200377","url":null,"abstract":"<p><strong>Background and objectives: </strong>In this study, we examine the long-term changes in chronic lesion tissue (CLT) among patients with relapsing-remitting MS (RRMS), focusing on its impact on clinical and radiologic disease progression indicators.</p><p><strong>Methods: </strong>The study involved 72 patients with multiple sclerosis with at least a 5-year follow-up. Annual assessments used 3D fluid-attenuated inversion recovery (FLAIR), precontrast and postcontrast 3D T1, and diffusion-weighted MRI. Lesion segmentation was conducted using iQ-MS software, while brain structures were segmented using AssemblyNet. Volumetric changes in CLT were tracked using a novel custom-designed pipeline that estimates longitudinal volumetric changes in CLT using serial MRI data.</p><p><strong>Results: </strong>Throughout the follow-up period, the volume of CLT in the entire cohort increased continuously and steadily, averaging 7.75% ± 8.2% or 315 ± 465 mm³ per year. Patients with expanding CLT experienced significantly faster brain atrophy, affecting both white and gray matter, particularly in the brain's central area. Expanded CLT was also associated with higher and worsening Expanded Disability Status Scale (EDSS) scores, in contrast to the stable CLT group, where EDSS remained unchanged. Sample size calculation for a clinical trial investigating the effect of treatment on slow expansion of chronic lesions demonstrated that a relatively small cohort of patients with RRMS, ranging from 24 to 69 patients per arm, would be required.</p><p><strong>Discussion: </strong>This study demonstrates that, over a period of up to 5 years, patient-specific enlargement of CLT, when present, progresses at a constant rate and significantly influences brain atrophy and disease progression. In addition, the study underscores CLT as a promising biomarker for RRMS progression and suggests the feasibility of smaller, targeted clinical trials to evaluate treatments aimed at reducing chronic lesion expansion.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 3","pages":"e200377"},"PeriodicalIF":7.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11908449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527882","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":"\"Will the Real Demyelinating Disorder Please Stand Up?\": From the National Multiple Sclerosis Society Case Conference Proceedings.","authors":"Aisha Elfasi, Myla D Goldman, Claire Riley, Scott S Zamvil, Scott Douglas Newsome","doi":"10.1212/NXI.0000000000200380","DOIUrl":"10.1212/NXI.0000000000200380","url":null,"abstract":"<p><p>A 46-year-old man presented with progressive painful monocular vision loss and left leg paresthesias. Workup demonstrated multifocal demyelinating lesions and CSF-restricted oligoclonal bands. He was diagnosed with multiple sclerosis (MS), but follow-up testing was notable for positive myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG). We discuss implications and clinical considerations for MOG-IgG positivity in MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 3","pages":"e200380"},"PeriodicalIF":7.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11896627/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597403","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":"Diagnostic Utility of Kappa Free Light Chain Index in Adults With Inaugural Optic Neuritis.","authors":"Sarah Demortiere, Natacha Stolowy, Marine Perriguey, Clemence Boutiere, Audrey Rico, Frederic Hilezian, Blaise-Roger Ndjomo-Ndjomo, Pierre Durozard, Jan-Patrick Stellmann, Romain Marignier, José Boucraut, Jean Pelletier, Adil Maarouf, Bertrand Audoin","doi":"10.1212/NXI.0000000000200386","DOIUrl":"10.1212/NXI.0000000000200386","url":null,"abstract":"<p><strong>Background and objectives: </strong>A simple, quick, and reproducible procedure for distinguishing multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD) at inaugural optic neuritis (ION) could be highly valuable in guiding early management.</p><p><strong>Methods: </strong>We included all adults admitted to the MS center of Marseille for ION between March 2016 and April 2024, with CSF analysis including the kappa free light chain (K-FLC) index. Receiver operating characteristic curves were used to measure the diagnostic ability of the K-FLC index.</p><p><strong>Results: </strong>Two hundred twenty-seven adults were admitted for ION; 210 (93%) had a K-FLC index measurement. MS was diagnosed in 84 (40%); clinically isolated syndrome suggestive of MS in 77 (36.5%), including 20 with future conversion to MS (CISwc); MOGAD in 26 (12.5%); NMOSD in 13 (6%); and other inflammatory disorders in 10 (5%). A K-FLC index ≥6.7 differentiated MS/CISwc from other diagnoses with specificity 86% and sensitivity 95% (area under the curve [AUC] 0.94). A K-FLC index <4.9 differentiated MOGAD from other diagnoses with specificity 63% and sensitivity 92% (AUC 0.78) and MOGAD from MS/CISwc with specificity 96% and sensitivity 92% (AUC 0.97). Among all patients, 93 (44%) had a K-FLC index <4.9: 24 of these (26%) had MOGAD and 5 (5.5%) MS/CISwc. Among the remaining patients with a K-FLC index ≥4.9 (n = 117), 2 (1.7%) had MOGAD (K-FLC index of 7.9 and 16.2) and 99 (85%) MS/CISwc. Among patients with normal MRI (n = 96), 73 (76%) had a K-FLC index <4.9: 22 of these (30%) had MOGAD, and none showed conversion to MS. Among the remaining patients with a K-FLC index ≥4.9 (n = 23), 2 (8.5%) had MOGAD and 7 (30.5%) showed conversion to MS. The K-FLC index did not differentiate NMOSD from other diagnoses and only moderately differentiated NMO from MS/CISwc (AUC 0.80).</p><p><strong>Discussion: </strong>The K-FLC index is an accessible biomarker to guide early diagnosis in patients with ION. The probability of MOGAD in patients with ION and a K-FLC index ≥4.9 is low even in case of normal brain/spinal cord MRI.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that for patients with ION, the K-FLC index can distinguish between MS/CISwc and MOGAD.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 3","pages":"e200386"},"PeriodicalIF":7.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630637","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":"Profile and Usefulness of Serum Cytokines to Predict Prognosis in Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease.","authors":"Javier Villacieros-Álvarez, Carmen Espejo, Georgina Arrambide, Alessandro Dinoto, Patricia Mulero, Laura Rubio-Flores, Pablo Nieto, Carmen Alcalá, Jose E Meca-Lallana, Jorge Millan-Pascual, Pedro Martínez-García, Raphael Bernard-Valnet, Inés González-Suárez, Aída Orviz, Raquel Téllez, Laura Navarro Cantó, Silvia Presas-Rodríguez, Sergio Martínez-Yélamos, Juan Pablo Cuello, Ana Alonso, Raquel Piñar Morales, Gary Álvarez Bravo, Lakhdar Benyahya, Sophie Trouillet-Assant, Virginie Dyon-Tafan, Caroline Froment Tilikete, Aurélie Ruet, Bertrand Bourre, Romain Deschamps, Caroline Papeix, Elisabeth Maillart, Philippe Kerschen, Xavier Ayrignac, Àlex Rovira, Cristina Auger, Bertrand Audoin, Xavier Montalban, Mar Tintore, Sara Mariotto, Alvaro Cobo-Calvo, Romain Marignier","doi":"10.1212/NXI.0000000000200401","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200401","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 3","pages":"e200401"},"PeriodicalIF":7.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11985168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003007","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":"White Matter Tract Degeneration in Multiple Sclerosis Patients With Progression Independent of Relapse Activity.","authors":"Mario Ocampo-Pineda, Alessandro Cagol, Pascal Benkert, Muhamed Barakovic, Po-Jui Lu, Jannis Müller, Sabine Anna Schaedelin, Lester Melie-Garcia, Matthias Weigel, Maria Pia Sormani, Ludwig Kappos, Jens Kuhle, Cristina Granziera","doi":"10.1212/NXI.0000000000200388","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200388","url":null,"abstract":"<p><strong>Background and objectives: </strong>Progression independent of relapse activity (PIRA) is associated with worse outcomes in people with multiple sclerosis (pwMS). Although previous research has linked PIRA to accelerated brain and spinal cord atrophy and compartmentalized chronic inflammation, the role of white matter (WM) tract degeneration remains unclear. This study aimed to explore the relationship between PIRA and the integrity of major WM tracts using diffusion tensor imaging (DTI).</p><p><strong>Methods: </strong>A cohort of 258 pwMS was stratified based on the presence or absence of PIRA over a 4-year follow-up period. At the end of follow-up, DTI metrics were compared between groups using propensity score-weighted linear regression models to account for potential confounders.</p><p><strong>Results: </strong>PwMS with ≥1 PIRA event (n = 39) exhibited significant reductions in fractional anisotropy and increases in radial, axial, and mean diffusivity within the corpus callosum and motor tracts (false discovery rate-adjusted <i>p</i> ≤ 0.04) compared with those without PIRA, indicating more pronounced WM damage.</p><p><strong>Discussion: </strong>Our findings highlight an association between PIRA and microstructural damage in key WM tracts. The observed DTI changes likely reflect processes such as Wallerian degeneration and contribute to the growing evidence linking PIRA to neurodegeneration.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 3","pages":"e200388"},"PeriodicalIF":7.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12007938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010166","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":"Conformational Antibodies to Proteolipid Protein-1 and Its Peripheral Isoform DM20 in Patients With CNS Autoimmune Demyelinating Disorders.","authors":"Stefano Masciocchi, Pietro Businaro, Giacomo Greco, Silvia Scaranzin, Antonio Malvaso, Chiara Morandi, Elisabetta Zardini, Mario Risi, Elisa Vegezzi, Luca Diamanti, Paola Bini, Sabrina Siquilini, Maria Pia Giannoccaro, Luana Morelli, Rocco Liguori, Francesco Patti, Valeria De Giuli, Emilio Portaccio, Chiara Zanetta, Stefania Bergamoni, Anna Maria Simone, Roberta Lanzillo, Giorgia Bruno, Antonio Gallo, Alvino Bisecco, Massimiliano Di Filippo, Flavia Pauri, Antonella Toriello, Paolo Barone, Francesco Tazza, Sebastiano Bucello, Paola Banfi, Martina Fabris, Irene Volonghi, Loredana Raciti, Maria Claudia Vigliani, Tommaso Bocci, Matteo Paoletti, Elena Colombo, Massimo Filippi, Anna Pichiecchio, Enrico Marchioni, Diego Franciotta, Matteo Gastaldi","doi":"10.1212/NXI.0000000000200389","DOIUrl":"10.1212/NXI.0000000000200389","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 3","pages":"e200389"},"PeriodicalIF":7.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11978436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674280","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 Association With AQP4-IgG-Positive Neuromyelitis Optica Spectrum Disorder in the Korean Population.","authors":"Jae-Won Hyun, Sinae Kim, Jangsup Moon, Na Young Park, You-Ri Kang, Ki Hoon Kim, Su-Hyun Kim, Ho Jin Kim","doi":"10.1212/NXI.0000000000200366","DOIUrl":"10.1212/NXI.0000000000200366","url":null,"abstract":"<p><strong>Background and objectives: </strong>Association of human leukocyte antigen (HLA) with anti-aquaporin-4 immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD) has been reported. However, this association in the Korean population has not been previously investigated. We aimed to evaluate whether specific HLA subtypes were associated with Korean patients with AQP4-IgG NMOSD and whether the HLA genotype is associated with specific clinical features.</p><p><strong>Methods: </strong>We compared the HLA subtypes of 122 patients with AQP4-IgG NMOSD with those of 485 (HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1) and 173 (HLA-DPB1) healthy controls. In addition, we compared the clinical features of patients with and without specific HLA genotypes.</p><p><strong>Results: </strong>The most significant risk allele for AQP4-IgG NMOSD was HLA-DRB1*03:01 (24 patients [19.67%], odds ratio [OR]: 3.997, <i>p</i>_c value = 0.0001). Susceptibility of AQP4-IgG NMOSD was significantly associated with the HLA-DRB1*03:01-DQB1*02:01 (23 patients [18.85%], OR: 3.792, <i>p</i>_c value = 0.0002) and DRB1*12:02-DQB1*03:01 (23 patients [18.85%], OR: 3.402, <i>p</i>_c value = 0.0009) haplotypes. Patients with the DRB1*12:02-DQB1*03:01 haplotype showed more frequent spinal involvement, a higher Expanded Disability Status Scale score at disease-onset nadir, and a shorter time to second attack than patients without this haplotype.</p><p><strong>Discussion: </strong>In a Korean cohort of patients withAQP4-IgG NMOSD, the HLA-DRB1*12:02-DQB1*03:01 haplotype was associated with disease severity at onset. HLA-DRB1*03:01, broadly reported as a significant susceptibility allele across diverse ethnic groups, showed a significant risk association in Korean patients with AQP4-IgG NMOSD.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"12 3","pages":"e200366"},"PeriodicalIF":7.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11876986/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527897","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}