Neurology(R) neuroimmunology & neuroinflammation最新文献

{"title":"Secondary Progressive Multiple Sclerosis: A Review of Clinical Characteristics, Definition, Prognostic Tools, and Disease-Modifying Therapies.","authors":"Tjalf Ziemssen,&nbsp;Virender Bhan,&nbsp;Jeremy Chataway,&nbsp;Tanuja Chitnis,&nbsp;Bruce Anthony Campbell Cree,&nbsp;Eva Kubala Havrdova,&nbsp;Ludwig Kappos,&nbsp;Pierre Labauge,&nbsp;Aaron Miller,&nbsp;Jin Nakahara,&nbsp;Celia Oreja-Guevara,&nbsp;Jacqueline Palace,&nbsp;Barry Singer,&nbsp;Maria Trojano,&nbsp;Ashwini Patil,&nbsp;Benedict Rauser,&nbsp;Thomas Hach","doi":"10.1212/NXI.0000000000200064","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200064","url":null,"abstract":"<p><p>Many challenges exist in the precise diagnosis and clinical management of secondary progressive multiple sclerosis (SPMS) because of the lack of definitive clinical, imaging, immunologic, or pathologic criteria that demarcate the transition from relapsing-remitting MS to SPMS. This review provides an overview of the diagnostic criteria/definition and the heterogeneity associated with different SPMS patient populations; it also emphasizes the importance of available prospective/retrospective tools to identify patients with SPMS earlier in the disease course so that approved disease-modifying therapies and nonpharmacological strategies will translate into better outcomes. Delivery of such interventions necessitates an evolving patient-clinician dialog within the context of a multidisciplinary team.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c9/ce/NXI-2022-200071.PMC9682625.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40506235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"More Efficient Complement Activation by Anti-Aquaporin-4 Compared With Anti-Myelin Oligodendrocyte Glycoprotein Antibodies.","authors":"Magdalena Lerch, Kathrin Schanda, Eliott Lafon, Reinhard Würzner, Sara Mariotto, Alessandro Dinoto, Eva Maria Wendel, Christian Lechner, Harald Hegen, Kevin Rostásy, Thomas Berger, Doris Wilflingseder, Romana Höftberger, Markus Reindl","doi":"10.1212/NXI.0000000000200059","DOIUrl":"10.1212/NXI.0000000000200059","url":null,"abstract":"<p><strong>Background and objectives: </strong>The objective was to study complement-mediated cytotoxicity induced by immunoglobulin G (IgG) anti-aquaporin-4 antibodies (AQP4-IgG) and anti-myelin oligodendrocyte glycoprotein antibodies (MOG-IgG) in human serum samples from patients suffering from the rare demyelinating diseases of the CNS neuromyelitis optica spectrum disorder (NMOSD) and MOG-IgG-associated disease (MOGAD).</p><p><strong>Methods: </strong>A cell-based assay with HEK293A cells expressing different MOG isoforms (MOGα_1-3β_1-3) or AQP4-M23 was used. Cells were incubated with human MOG-IgG or AQP4-IgG-positive serum samples together with active or heat-inactivated human complement, and complement-dependent cytotoxicity (CDC) was measured with a lactate dehydrogenase assay. To further quantify antibody-mediated cell damage, formation of the terminal complement complex (TCC) was analyzed by flow cytometry. In addition, immunocytochemistry of the TCC and complement component 3 (C3) was performed.</p><p><strong>Results: </strong>AQP4-IgG-positive serum samples induced higher CDC and TCC levels than MOG-IgG-positive sera. Notably, both showed a correlation between antibody titers and CDC and also between titers and TCC levels. In addition, all 6 MOG isoforms tested (MOGα_1-3β_1-3) could induce at least some CDC; however, the strongest MOG-IgG-induced CDC levels were found on MOGα₁, MOGα₃, and MOGβ₁. Different MOG-IgG binding patterns regarding recognition of different MOG isoforms were investigated, and it was found that MOG-IgG recognizing all 6 isoforms again induced highest CDC levels on MOGα₁ and MOGβ₁. Furthermore, surface staining of TCC and C3 revealed positive staining on all 6 MOG isoforms tested, as well as on AQP4-M23.</p><p><strong>Discussion: </strong>Both MOG-IgG and AQP4-IgG are able to induce CDC in a titer-dependent manner. However, AQP4-IgG showed markedly higher levels of CDC compared with MOG in vitro on target cells. This further highlights the role of complement in AQP4-IgG-mediated disease and diminishes the importance of complement activation in MOG-IgG-mediated autoimmune disease.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40506234","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kappa Free Light Chain Biomarkers Are Efficient for the Diagnosis of Multiple Sclerosis: A Large Multicenter Cohort Study.","authors":"Michael Levraut,&nbsp;Sabine Laurent-Chabalier,&nbsp;Xavier Ayrignac,&nbsp;Kévin Bigaut,&nbsp;Manon Rival,&nbsp;Sanae Squalli,&nbsp;Hélène Zéphir,&nbsp;Tifanie Alberto,&nbsp;Jean-David Pekar,&nbsp;Jonathan Ciron,&nbsp;Damien Biotti,&nbsp;Bénédicte Puissant-Lubrano,&nbsp;Jean-Philippe Camdessanché,&nbsp;Yannick Tholance,&nbsp;Olivier Casez,&nbsp;Bertrand Toussaint,&nbsp;Jeanne Marion,&nbsp;Thibault Moreau,&nbsp;Daniela Lakomy,&nbsp;Audrey Thomasset,&nbsp;Elisabeth Maillart,&nbsp;Delphine Sterlin,&nbsp;Aude Maurousset,&nbsp;Auriane Rocher,&nbsp;David Axel Laplaud,&nbsp;Edith Bigot-Corbel,&nbsp;Pierre-Olivier Bertho,&nbsp;Jean Pelletier,&nbsp;Joseph Boucraut,&nbsp;Pierre Labauge,&nbsp;Thierry Vincent,&nbsp;Jérôme De Sèze,&nbsp;Isabelle Jahn,&nbsp;Barbara Seitz-Polski,&nbsp;Eric Thouvenot,&nbsp;Christine Lebrun-Frenay","doi":"10.1212/NXI.0000000000200049","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200049","url":null,"abstract":"<p><strong>Background and objectives: </strong>Kappa free light chains (KFLC) seem to efficiently diagnose MS. However, extensive cohort studies are lacking to establish consensus cut-offs, notably to rule out non-MS autoimmune CNS disorders. Our objectives were to (1) determine diagnostic performances of CSF KFLC, KFLC index, and KFLC intrathecal fraction (IF) threshold values that allow us to separate MS from different CNS disorder control populations and compare them with oligoclonal bands' (OCB) performances and (2) to identify independent factors associated with KFLC quantification in MS.</p><p><strong>Methods: </strong>We conducted a retrospective multicenter study involving 13 French MS centers. Patients were included if they had a noninfectious and nontumoral CNS disorder, eligible data concerning CSF and serum KFLC, albumin, and OCB. Patients were classified into 4 groups according to their diagnosis: MS, clinically isolated syndrome (CIS), other inflammatory CNS disorders (OIND), and noninflammatory CNS disorder controls (NINDC).</p><p><strong>Results: </strong>One thousand six hundred twenty-one patients were analyzed (675 MS, 90 CIS, 297 OIND, and 559 NINDC). KFLC index and KFLC IF had similar performances in diagnosing MS from nonselected controls and OIND (<i>p</i> = 0.123 and <i>p</i> = 0.991 for area under the curve [AUC] comparisons) and performed better than CSF KFLC (<i>p</i> < 0.001 for all AUC comparisons). A KFLC index of 8.92 best separated MS/CIS from the entire nonselected control population, with better performances than OCB (<i>p</i> < 0.001 for AUC comparison). A KFLC index of 11.56 best separated MS from OIND, with similar performances than OCB (<i>p</i> = 0.065). In the multivariate analysis model, female gender (<i>p</i> = 0.003), young age (<i>p</i> = 0.013), and evidence of disease activity (<i>p</i> < 0.001) were independent factors associated with high KFLC index values in patients with MS, whereas MS phenotype, immune-modifying treatment use at sampling, and the FLC analyzer type did not influence KFLC index.</p><p><strong>Discussion: </strong>KFLC biomarkers are efficient tools to separate patients with MS from controls, even when compared with other patients with CNS autoimmune disorder. Given these results, we suggest using KFLC index or KFLC IF as a criterion to diagnose MS.</p><p><strong>Classification of evidence: </strong>This study provides Class III evidence that KFLC index or IF can be used to differentiate patients with MS from nonselected controls and from patients with other autoimmune CNS disorders.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/ba/NXI-2022-200056.PMC9663206.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40702673","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurofilament Light Chain Levels Are Predictive of Clinical Conversion in Radiologically Isolated Syndrome.","authors":"Manon Rival,&nbsp;Eric Thouvenot,&nbsp;Lucile Du Trieu de Terdonck,&nbsp;Sabine Laurent-Chabalier,&nbsp;Christophe Demattei,&nbsp;Ugur Uygunoglu,&nbsp;Giovanni Castelnovo,&nbsp;Mikael Cohen,&nbsp;Darin T Okuda,&nbsp;Orhun H Kantarci,&nbsp;Daniel Pelletier,&nbsp;Christina Azevedo,&nbsp;Philippe Marin,&nbsp;Sylvain Lehmann,&nbsp;Aksel Siva,&nbsp;Thibault Mura,&nbsp;Christine Lebrun-Frenay","doi":"10.1212/NXI.0000000000200044","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200044","url":null,"abstract":"<p><strong>Background and objectives: </strong>To evaluate the predictive value of serum neurofilament light chain (sNfL) and CSF NfL (cNfL) in patients with radiologically isolated syndrome (RIS) for evidence of disease activity (EDA) and clinical conversion (CC).</p><p><strong>Methods: </strong>sNfL and cNfL were measured at RIS diagnosis by single-molecule array (Simoa). The risk of EDA and CC according to sNfL and cNfL was evaluated using the Kaplan-Meier analysis and multivariate Cox regression models including age, spinal cord (SC) or infratentorial lesions, oligoclonal bands, CSF chitinase 3-like protein 1, and CSF white blood cells.</p><p><strong>Results: </strong>Sixty-one patients with RIS were included. At diagnosis, sNfL and cNfL were correlated (Spearman r = 0.78, <i>p</i> < 0.001). During follow-up, 47 patients with RIS showed EDA and 36 patients showed CC (median time 12.6 months, 1-86). When compared with low levels, medium and high cNfL (>260 pg/mL) and sNfL (>5.0 pg/mL) levels were predictive of EDA (log rank, <i>p</i> < 0.01 and <i>p</i> = 0.02, respectively). Medium-high cNfL levels were predictive of CC (log rank, <i>p</i> < 0.01). In Cox regression models, cNfL and sNfL were independent factors of EDA, while SC lesions, cNfL, and sNfL were independent factors of CC.</p><p><strong>Discussion: </strong>cNfL >260 pg/mL and sNfL >5.0 pg/mL at diagnosis are independent predictive factors of EDA and CC in RIS. Although cNfL predicts disease activity better, sNfL is more accessible than cNfL and can be considered when a lumbar puncture is not performed.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that in people with radiologic isolated syndrome (RIS), initial serum and CSF NfL levels are associated with subsequent evidence of disease activity or clinical conversion.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/53/86/NXI-2022-200051.PMC9621336.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40569844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early Reduction of MRI Activity During 6 Months of Cladribine Tablet Treatment for Highly Active Relapsing Multiple Sclerosis: MAGNIFY-MS.","authors":"","doi":"10.1212/NXI.0000000000200061","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200061","url":null,"abstract":"","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9585483/pdf/NXI-2022-200068.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40558737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patients With Severe Multiple Sclerosis Exhibit Functionally Altered CD8⁺ Regulatory T Cells.","authors":"Nail Benallegue,&nbsp;Bryan Nicol,&nbsp;Juliette Lasselin,&nbsp;Severine Bézie,&nbsp;Lea Flippe,&nbsp;Hadrien Regue,&nbsp;Nadege Vimond,&nbsp;Severine Remy,&nbsp;Alexandra Garcia,&nbsp;Fabienne Le Frère,&nbsp;Ignacio Anegon,&nbsp;David Laplaud,&nbsp;Carole Guillonneau","doi":"10.1212/NXI.0000000000200016","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200016","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the CNS. Studies of immune dysfunction in MS have mostly focused on CD4&lt;sup&gt;+&lt;/sup&gt; Tregs, but the role of CD8&lt;sup&gt;+&lt;/sup&gt; Tregs remains largely unexplored. We previously evidenced the suppressive properties of rat and human CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low/neg&lt;/sup&gt; Tregs from healthy individuals, expressing Forkhead box P3 (FOXP3) and acting through interferon-gamma (IFN-γ), transforming growth factor beta (TGFβ), and interleukin-34 (IL-34). secretions to regulate immune responses and control diseases such as transplant rejection. To better understand CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low/neg&lt;/sup&gt; Tregs contribution to MS pathology, we further investigated their phenotype, function, and transcriptome in patients with MS.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We enrolled adults with relapsing-remitting MS and age-matched and sex-matched healthy volunteers (HVs). CD8&lt;sup&gt;+&lt;/sup&gt; T cells were segregated based on low or lack of expression of CD45RC. First, the frequency in CSF and blood, phenotype, transcriptome, and function of CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;/sup&gt; and &lt;sup&gt;neg&lt;/sup&gt; were investigated according to exacerbation status and secondarily, according to clinical severity based on the MS severity score (MSSS) in patients with nonexacerbating MS. We then induced active MOG&lt;sub&gt;35-55&lt;/sub&gt; EAE in C57Bl/6 mice and performed adoptive transfer of fresh and expanded CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;neg&lt;/sup&gt; Tregs to assess their ability to mitigate neuroinflammation in vivo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Thirty-one untreated patients with relapsing-remitting MS were compared with 40 age-matched and sex-matched HVs. We demonstrated no difference of CSF CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;/sup&gt; and CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;neg&lt;/sup&gt; proportions, but blood CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;/sup&gt; frequency was lower in patients with MS exacerbation when compared with that in HVs. CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;neg&lt;/sup&gt; Tregs but not CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;/sup&gt; showed higher suppressive capacities in vitro in MS patients with exacerbation than in patients without acute inflammatory attack. In vitro functional assays showed a compromised suppression capacity of CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;/sup&gt; Tregs in patients with nonexacerbating severe MS, defined by the MSSS. We then characterized murine CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;neg&lt;/sup&gt; Tregs and demonstrated the potential of CD45RC&lt;sup&gt;neg&lt;/sup&gt; cells to migrate to the CNS and mitigate experimental autoimmune encephalomyelitis in vivo.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;Altogether, these results suggest a defect in the number and function of CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;/sup&gt; Tregs during MS relapse and an association of CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low&lt;/sup&gt; Tregs dysfunction with MS severity. Thus, CD8&lt;sup&gt;+&lt;/sup&gt;CD45RC&lt;sup&gt;low/neg&lt;/sup&gt; T cells might bring new insights into the pathophysiology and new therap","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3c/7e/NXI-2022-200022.PMC9621606.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40558735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple Sclerosis CSF Is Enriched With Follicular T Cells Displaying a Th1/Eomes Signature.","authors":"Jérémy Morille,&nbsp;Marion Mandon,&nbsp;Stéphane Rodriguez,&nbsp;David Roulois,&nbsp;Simon Leonard,&nbsp;Alexandra Garcia,&nbsp;Sandrine Wiertlewski,&nbsp;Emmanuelle Le Page,&nbsp;Laureline Berthelot,&nbsp;Arnaud Nicot,&nbsp;Camille Mathé,&nbsp;Flora Lejeune,&nbsp;Karin Tarte,&nbsp;Céline Delaloy,&nbsp;Patricia Amé,&nbsp;David Laplaud,&nbsp;Laure Michel","doi":"10.1212/NXI.0000000000200033","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200033","url":null,"abstract":"<p><strong>Background and objectives: </strong>Tertiary lymphoid structures and aggregates are reported in the meninges of patients with multiple sclerosis (MS), especially at the progressive stage, and are strongly associated with cortical lesions and disability. Besides B cells, these structures comprise follicular helper T (Tfh) cells that are crucial to support B-cell differentiation. Tfh cells play a pivotal role in amplifying autoreactive B cells and promoting autoantibody production in several autoimmune diseases, but very few are known in MS. In this study, we examined the phenotype, frequency, and transcriptome of circulating cTfh cells in the blood and CSF of patients with relapsing-remitting MS (RRMS).</p><p><strong>Methods: </strong>The phenotype and frequency of cTfh cells were analyzed in the blood of 39 healthy controls and 41 untreated patients with RRMS and in the CSF and paired blood of 10 patients with drug-naive RRMS at diagnosis by flow cytometry. Using an in vitro model of blood-brain barrier, we assessed the transendothelial migratory abilities of the different cTfh-cell subsets. Finally, we performed an RNA sequencing analysis of paired CSF cTfh cells and blood cTfh cells in 8 patients sampled at their first demyelinating event.</p><p><strong>Results: </strong>The blood phenotype and frequency of cTfh cells were not significantly modified in patients with RRMS. In the CSF, we found an important infiltration of Tfh1 cells, with a high proportion of activated PD1⁺ cells. We demonstrated that the specific subset of Tfh1 cells presents increased migration abilities to cross an in vitro model of blood-brain barrier. Of interest, even at the first demyelinating event, cTfh cells in the CSF display specific characteristics with upregulation of <i>EOMES</i> gene and proinflammatory/cytotoxic transcriptomic signature able to efficiently distinguish cTfh cells from the CSF and blood. Finally, interactome analysis revealed potential strong cross talk between pathogenic B cells and CSF cTfh cells, pointing out the CSF as opportune supportive compartment and highlighting the very early implication of B-cell helper T cells in MS pathogenesis.</p><p><strong>Discussion: </strong>Overall, CSF enrichment in activated Tfh1 as soon as disease diagnosis, associated with high expression of EOMES, and a predicted high propensity to interact with CSF B cells suggest that these cells probably contribute to disease onset and/or activity.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/47/3a/NXI-2022-200039.PMC9585484.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40558736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease Presenting as Intracranial Hypertension: A Case Report.","authors":"Jaydip Ray Chaudhuri,&nbsp;Jui Jade Bagul,&nbsp;Alluri Swathi,&nbsp;Bhim Sen Singhal,&nbsp;N Chakradhar Reddy,&nbsp;Kiran Kumar Vallam","doi":"10.1212/NXI.0000000000200020","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200020","url":null,"abstract":"<p><p>The production of autoantibodies against myelin oligodendrocyte glycoprotein (MOG) can cause a spectrum of autoimmune disorders, including optic neuritis, transverse myelitis, brainstem encephalitis, and acute disseminated encephalomyelitis. In this study, we present the case of a 19-year-old woman with an unusual clinical presentation of intracranial hypertension (IH) and bilateral papilledema. The patient presented with symptoms of increased intracranial pressure, which followed a relapsing, remitting course over several months. Serial CSF studies showed an increased opening pressure during clinical relapses. The CSF and serum tested positive for MOG immunoglobulin G antibodies. Contrast-enhanced MRI of the brain showed mild meningeal enhancement in the left parietal region with subtle underlying cortical hyperintensities, indicating possible fluid-attenuated inversion recovery variable unilateral enhancement of the leptomeninges. The patient responded well to immunosuppressive therapy using rituximab. The presentation of MOG antibody-associated disease (MOGAD) as IH without optic neuritis is rare. This report presents the first description of a relapsing remitting course presenting each time with only symptoms of raised intracranial pressure, without developing any typical clinical manifestations of MOGAD.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7f/3f/NXI-2022-200026.PMC9581460.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40343198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging Characteristics of Choroid Plexuses in Presymptomatic Multiple Sclerosis: A Retrospective Study.","authors":"Vito A G Ricigliano,&nbsp;Céline Louapre,&nbsp;Emilie Poirion,&nbsp;Annalisa Colombi,&nbsp;Arya Yazdan Panah,&nbsp;Andrea Lazzarotto,&nbsp;Emanuele Morena,&nbsp;Elodie Martin,&nbsp;Michel Bottlaender,&nbsp;Benedetta Bodini,&nbsp;Danielle Seilhean,&nbsp;Bruno Stankoff","doi":"10.1212/NXI.0000000000200026","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200026","url":null,"abstract":"<p><strong>Background and objectives: </strong>Recent imaging studies have suggested a possible involvement of the choroid plexus (CP) in multiple sclerosis (MS). Here, we investigated whether CP changes are already detectable at the earliest stage of MS, preceding symptom onset.</p><p><strong>Methods: </strong>This study is a retrospective analysis of 27 patients with presymptomatic MS, 97 patients with clinically definite MS (CDMS), and 53 healthy controls (HCs) who underwent a cross-sectional 3T-MRI acquisition; of which, 22 MS, 19 HCs, and 1 presymptomatic MS (evaluated 8 months before conversion to CDMS) also underwent translocator protein (TSPO) ¹⁸F-DPA-714 PET and were included in the analysis. CPs were manually segmented on 3D T1-weighted images for volumetric analysis. CP ¹⁸F-DPA-714 uptake, reflecting inflammation, was calculated as the average standardized uptake value (SUV). Multivariable regressions adjusted for age, sex, and ventricular and brain volume were fitted to test CP volume differences between presymptomatic patients and MS or HCs. For the presymptomatic case who also had ¹⁸F-DPA-714 PET, CP SUV differences with MS and HCs were assessed through Crawford-Howell tests. To provide further insight into the interpretation of ¹⁸F-DPA-714-PET uptake at the CP level, a postmortem analysis of CPs in MS vs HCs was performed to characterize the cellular localization of TSPO expression.</p><p><strong>Results: </strong>Compared with HCs, patients with presymptomatic MS had 32% larger CPs (β = 0.38, <i>p</i> = 0.001), which were not dissimilar to MS CPs (<i>p</i> = 0.69). Moreover, in the baseline scan of the presymptomatic case who later on developed MS, TSPO PET showed 33% greater CP inflammation vs HCs (<i>p</i> = 0.04), although no differences in ¹⁸F-DPA-714 uptake were found in parenchymal regions vs controls. CP postmortem analysis identified a population of CD163⁺ mononuclear phagocytes expressing TSPO in MS, possibly contributing to the increased ¹⁸F-DPA-714 uptake.</p><p><strong>Discussion: </strong>We identified an imaging signature in CPs at the presymptomatic MS stage using MRI; in addition, we found an increased CP inflammation with PET in a single presymptomatic patient. These findings suggest a role of CP imaging as an early biomarker and argue for the involvement of the blood-CSF barrier dysfunction in disease development.</p><p><strong>Trial registration information: </strong>APHP-20210727144630, EudraCT-Number: 2008-004174-40; ClinicalTrials.gov: NCT02305264, NCT01651520, and NCT02319382.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/dd/50/NXI-2022-200032.PMC9562043.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33505457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B-Cell Reconstitution After Autologous Hematopoietic Stem Cell Transplantation in Multiple Sclerosis.","authors":"Valentin von Niederhäusern,&nbsp;Josefine Ruder,&nbsp;Marie Ghraichy,&nbsp;Ilijas Jelcic,&nbsp;Antonia Maria Müller,&nbsp;Urs Schanz,&nbsp;Roland Martin,&nbsp;Johannes Trück","doi":"10.1212/NXI.0000000000200027","DOIUrl":"https://doi.org/10.1212/NXI.0000000000200027","url":null,"abstract":"Background and Objectives Autologous hematopoietic stem cell transplantation (aHSCT) is increasingly used to treat aggressive forms of multiple sclerosis (MS). This procedure is believed to result in an immune reset and restoration of a self-tolerant immune system. Immune reconstitution has been extensively studied for T cells, but only to a limited extent for B cells. As increasing evidence suggests an important role of B cells in MS pathogenesis, we sought here to better understand reconstitution and the extent of renewal of the B-cell system after aHSCT in MS. Methods Using longitudinal multidimensional flow cytometry and immunoglobulin heavy chain (IgH) repertoire sequencing following aHSCT with BCNU + Etoposide + Ara-C + Melphalan anti-thymocyte globulin, we analyzed the B-cell compartment in a cohort of 20 patients with MS in defined intervals before and up to 1 year after aHSCT and compared these findings with data from healthy controls. Results Total B-cell numbers recovered within 3 months and increased above normal levels 1 year after transplantation, successively shifting from a predominantly transitional to a naive immune phenotype. Memory subpopulations recovered slowly and remained below normal levels with reduced repertoire diversity 1 year after transplantation. Isotype subclass analysis revealed a proportional shift toward IgG1-expressing cells and a reduction in IgG2 cells. Mutation analysis of IgH sequences showed that highly mutated memory B cells and plasma cells may transiently survive conditioning while the analysis of sequence cluster overlap, variable (IGHV) and joining (IGHJ) gene usage and repertoire diversity suggested a renewal of the late posttransplant repertoire. In patients with early cytomegalovirus reactivation, reconstitution of naive and memory B cells was delayed. Discussion Our detailed characterization of B-cell reconstitution after aHSCT in MS indicates a reduced reactivation potential of memory B cells up to 1 year after transplantation, which may leave patients susceptible to infection, but may also be an important aspect of its mechanism of action.","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2022-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c6/1f/NXI-2022-200033.PMC9562041.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33506342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}