Neurology(R) neuroimmunology & neuroinflammation最新文献

{"title":"Nicolau Syndrome After Glatiramer Acetate Injection in Close Proximity to Administration of SARS-CoV-2 mRNA Vaccine.","authors":"Michael Yu Sy, Erin Fromm, Linda Doan, Nathan Rojek, Alexander Ulrich Brandt","doi":"10.1212/NXI.0000000000001112","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001112","url":null,"abstract":"Nicolau syndrome (synonym: embolia cutis medicamentosa) is a rare complication of subcutaneous and IM drug injections, typically independent of the drug itself. Patients develop painful purpuric and necrotizing lesions at the injection site, often requiring surgical intervention. The pathogenesis of the ischemic skin necrosis is poorly understood. We report 2 cases of skin necrosis associated with injection of glatiramer acetate (GA) in patients with multiple sclerosis (MS), which occurred in close temporal relation to the second dose of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) mRNA vaccine.","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/be/f8/NEURIMMINFL2021039063.PMC8587730.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39875188","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":"Targeted RNA Sequencing of VZV-Infected Brain Vascular Adventitial Fibroblasts Indicates That Amyloid May Be Involved in VZV Vasculopathy.","authors":"Andrew N Bubak,&nbsp;Christina N Como,&nbsp;James E Hassell,&nbsp;Teresa Mescher,&nbsp;Seth E Frietze,&nbsp;Christy S Niemeyer,&nbsp;Randall J Cohrs,&nbsp;Maria A Nagel","doi":"10.1212/NXI.0000000000001103","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001103","url":null,"abstract":"<p><strong>Background and objectives: </strong>Compared with stroke controls, patients with varicella zoster virus (VZV) vasculopathy have increased amyloid in CSF, along with increased amylin (islet amyloid polypeptide [IAPP]) and anti-VZV antibodies. Thus, we examined the gene expression profiles of VZV-infected primary human brain vascular adventitial fibroblasts (HBVAFs), one of the initial arterial cells infected in VZV vasculopathy, to determine whether they are a potential source of amyloid that can disrupt vasculature and potentiate inflammation.</p><p><strong>Methods: </strong>Mock- and VZV-infected quiescent HBVAFs were harvested at 3 days postinfection. Targeted RNA sequencing of the whole-human transcriptome (BioSpyder Technologies, TempO-Seq) was conducted followed by gene set enrichment and pathway analysis. Selected pathways unique to VZV-infected cells were confirmed by enzyme-linked immunoassays, migration assays, and immunofluorescence analysis (IFA) that included antibodies against amylin and amyloid-beta, as well as amyloid staining by Thioflavin-T.</p><p><strong>Results: </strong>Compared with mock, VZV-infected HBVAFs had significantly enriched gene expression pathways involved in vascular remodeling and vascular diseases; confirmatory studies showed secretion of matrix metalloproteinase-3 and -10, as well increased migration of infected cells and uninfected cells when exposed to conditioned media from VZV-infected cells. In addition, significantly enriched pathways involved in amyloid-associated diseases (diabetes mellitus, amyloidosis, and Alzheimer disease), tauopathy, and progressive neurologic disorder were identified; predicted upstream regulators included amyloid precursor protein, apolipoprotein E, microtubule-associated protein tau, presenilin 1, and IAPP. Confirmatory IFA showed that VZV-infected HBVAFs contained amyloidogenic peptides (amyloid-beta and amylin) and intracellular amyloid.</p><p><strong>Discussion: </strong>Gene expression profiles and pathway enrichment analysis of VZV-infected HBVAFs, as well as phenotypic studies, reveal features of pathologic vascular remodeling (e.g., increased cell migration and changes in the extracellular matrix) that can contribute to cerebrovascular disease. Furthermore, the discovery of amyloid-associated transcriptional pathways and intracellular amyloid deposition in HBVAFs raise the possibility that VZV vasculopathy is an amyloid disease. Amyloid deposition may contribute to cell death and loss of vascular wall integrity, as well as potentiate chronic inflammation in VZV vasculopathy, with disease severity and recurrence determined by the host's ability to clear virus infection and amyloid deposition and by the coexistence of other amyloid-associated diseases (i.e., Alzheimer disease and diabetes mellitus).</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/36/93/NEURIMMINFL2021039266.PMC8587729.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39875184","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":"Anti-C2 Antibody ARGX-117 Inhibits Complement in a Disease Model for Multifocal Motor Neuropathy.","authors":"Kevin Budding,&nbsp;Lill Eva Johansen,&nbsp;Inge Van de Walle,&nbsp;Kim Dijkxhoorn,&nbsp;Elisabeth de Zeeuw,&nbsp;Lauri M Bloemenkamp,&nbsp;Jeroen W Bos,&nbsp;Marc D Jansen,&nbsp;Chantall A D Curial,&nbsp;Karen Silence,&nbsp;Hans de Haard,&nbsp;Christophe Blanchetot,&nbsp;Liesbeth Van de Ven,&nbsp;Jeanette H W Leusen,&nbsp;R Jeroen Pasterkamp,&nbsp;Leonard H van den Berg,&nbsp;C Erik Hack,&nbsp;Peter Boross,&nbsp;W Ludo van der Pol","doi":"10.1212/NXI.0000000000001107","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001107","url":null,"abstract":"<p><strong>Background and objectives: </strong>To determine the role of complement in the disease pathology of multifocal motor neuropathy (MMN), we investigated complement activation, and inhibition, on binding of MMN patient-derived immunoglobulin M (IgM) antibodies in an induced pluripotent stem cell (iPSC)-derived motor neuron (MN) model for MMN.</p><p><strong>Methods: </strong>iPSC-derived MNs were characterized for the expression of complement receptors and membrane-bound regulators, for the binding of circulating IgM anti-GM1 from patients with MMN, and for subsequent fixation of C4 and C3 on incubation with fresh serum. The potency of ARGX-117, a novel inhibitory monoclonal antibody targeting C2, to inhibit fixation of complement was assessed.</p><p><strong>Results: </strong>iPSC-derived MNs moderately express the complement regulatory proteins CD46 and CD55 and strongly expressed CD59. Furthermore, MNs express C3aR, C5aR, and complement receptor 1. IgM anti-GM1 antibodies in serum from patients with MMN bind to MNs and induce C3 and C4 fixation on incubation with fresh serum. ARGX-117 inhibits complement activation downstream of C4 induced by patient-derived anti-GM1 antibodies bound to MNs.</p><p><strong>Discussion: </strong>Binding of IgM antibodies from patients with MMN to iPSC-derived MNs induces complement activation. By expressing complement regulatory proteins, particularly CD59, MNs are protected against complement-mediated lysis. Yet, because of expressing C3aR, the function of these cells may be affected by complement activation upstream of membrane attack complex formation. ARGX-117 inhibits complement activation upstream of C3 in this disease model for MMN and therefore represents an intervention strategy to prevent harmful effects of complement in MMN.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ae/4e/NEURIMMINFL2020038520.PMC8587732.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39875185","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":"Decrease in Serum Anti-MAG Autoantibodies Is Associated With Therapy Response in Patients With Anti-MAG Neuropathy: Retrospective Study.","authors":"Pascal Hänggi,&nbsp;Butrint Aliu,&nbsp;Kea Martin,&nbsp;Ruben Herrendorff,&nbsp;Andreas Johann Steck","doi":"10.1212/NXI.0000000000001109","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001109","url":null,"abstract":"<p><strong>Background and objectives: </strong>The objective of the retrospective analysis was to test the hypothesis that changes in serum anti-myelin-associated glycoprotein (MAG) autoantibodies are associated with clinical response to immunotherapy in patients with anti-MAG neuropathy.</p><p><strong>Methods: </strong>As of January 29, 2020, we used anti-myelin-associated glycoprotein-related search strings in the Medline database to identify studies that provided information on anti-MAG immunoglobulin M (IgM) autoantibodies and clinical outcomes during immunotherapies. The relative change in anti-MAG IgM titers, paraprotein levels, or total IgM was determined before, during, or posttreatment, and the patients were assigned to \"responder,\" \"nonresponder,\"' or \"acute deteriorating\" category depending on their clinical response to treatment. The studies were qualified as \"supportive\" or \"not supportive\" depending on the percentage of patients exhibiting an association between relative change of anti-MAG antibody titers or levels and change in clinical outcomes.</p><p><strong>Results: </strong>Fifty studies with 410 patients with anti-MAG neuropathy were included in the analysis. Forty studies with 303 patients supported the hypothesis that a \"responder\" patient had a relative reduction of anti-MAG antibody titers or levels that is associated with clinical improvements and \"nonresponder\" patients exhibited no significant change in anti-MAG IgM antibodies. Six studies with 93 patients partly supported, and 4 studies with 26 patients did not support the hypothesis.</p><p><strong>Discussion: </strong>The retrospective analysis confirmed the hypothesis that a relative reduction in serum anti-MAG IgM antibodies is associated with a clinical response to immunotherapies; a sustained reduction of at least 50% compared with pretreatment titers or levels could be a valuable indicator for therapeutic response.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/52/26/NEURIMMINFL2020027250.PMC8587733.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39875187","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":"COVID-19 Severity in Multiple Sclerosis: Putting Data Into Context.","authors":"Maria Pia Sormani,&nbsp;Irene Schiavetti,&nbsp;Luca Carmisciano,&nbsp;Cinzia Cordioli,&nbsp;Massimo Filippi,&nbsp;Marta Radaelli,&nbsp;Paolo Immovilli,&nbsp;Marco Capobianco,&nbsp;Nicola De Rossi,&nbsp;Giampaolo Brichetto,&nbsp;Eleonora Cocco,&nbsp;Cinzia Scandellari,&nbsp;Paola Cavalla,&nbsp;Ilaria Pesci,&nbsp;Antonio Zito,&nbsp;Paolo Confalonieri,&nbsp;Girolama Alessandra Marfia,&nbsp;Paola Perini,&nbsp;Matilde Inglese,&nbsp;Maria Trojano,&nbsp;Vincenzo Brescia Morra,&nbsp;Gioacchino Tedeschi,&nbsp;Giancarlo Comi,&nbsp;Mario Alberto Battaglia,&nbsp;Francesco Patti,&nbsp;Marco Salvetti","doi":"10.1212/NXI.0000000000001105","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001105","url":null,"abstract":"<p><strong>Background and objectives: </strong>It is unclear how multiple sclerosis (MS) affects the severity of COVID-19. The aim of this study is to compare COVID-19-related outcomes collected in an Italian cohort of patients with MS with the outcomes expected in the age- and sex-matched Italian population.</p><p><strong>Methods: </strong>Hospitalization, intensive care unit (ICU) admission, and death after COVID-19 diagnosis of 1,362 patients with MS were compared with the age- and sex-matched Italian population in a retrospective observational case-cohort study with population-based control. The observed vs the expected events were compared in the whole MS cohort and in different subgroups (higher risk: Expanded Disability Status Scale [EDSS] score > 3 or at least 1 comorbidity, lower risk: EDSS score ≤ 3 and no comorbidities) by the χ² test, and the risk excess was quantified by risk ratios (RRs).</p><p><strong>Results: </strong>The risk of severe events was about twice the risk in the age- and sex-matched Italian population: RR = 2.12 for hospitalization (<i>p</i> < 0.001), RR = 2.19 for ICU admission (<i>p</i> < 0.001), and RR = 2.43 for death (<i>p</i> < 0.001). The excess of risk was confined to the higher-risk group (n = 553). In lower-risk patients (n = 809), the rate of events was close to that of the Italian age- and sex-matched population (RR = 1.12 for hospitalization, RR = 1.52 for ICU admission, and RR = 1.19 for death). In the lower-risk group, an increased hospitalization risk was detected in patients on anti-CD20 (RR = 3.03, <i>p</i> = 0.005), whereas a decrease was detected in patients on interferon (0 observed vs 4 expected events, <i>p</i> = 0.04).</p><p><strong>Discussion: </strong>Overall, the MS cohort had a risk of severe events that is twice the risk than the age- and sex-matched Italian population. This excess of risk is mainly explained by the EDSS score and comorbidities, whereas a residual increase of hospitalization risk was observed in patients on anti-CD20 therapies and a decrease in people on interferon.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/5d/05/NEURIMMINFL2021039283.PMC8579249.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39857930","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":"COVID-19 Vaccination Reactogenicity in Persons With Multiple Sclerosis.","authors":"Farren Basil Shaw Briggs,&nbsp;Farrah J Mateen,&nbsp;Hollie Schmidt,&nbsp;Keisha M Currie,&nbsp;Heather M Siefers,&nbsp;Slavka Crouthamel,&nbsp;Bruce F Bebo,&nbsp;Julie Fiol,&nbsp;Michael K Racke,&nbsp;Kevin C O'Connor,&nbsp;Laura G Kolaczkowski,&nbsp;Phyllis Klein,&nbsp;Sara Loud,&nbsp;Robert Nicholas McBurney","doi":"10.1212/NXI.0000000000001104","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001104","url":null,"abstract":"<p><strong>Background and objectives: </strong>There are limited data on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine reactogenicity in persons with multiple sclerosis (PwMS) and how reactogenicity is affected by disease-modifying therapies (DMTs). The objective of this retrospective cross-sectional study was to generate real-world multiple sclerosis-specific vaccine safety information, particularly in the context of specific DMTs, and provide information to mitigate specific concerns in vaccine hesitant PwMS.</p><p><strong>Methods: </strong>Between 3/2021 and 6/2021, participants in iConquerMS, an online people-powered research network, reported SARS-CoV-2 vaccines, experiences of local (itch, pain, redness, swelling, or warmth at injection site) and systemic (fever, chills, fatigue, headache, joint pain, malaise, muscle ache, nausea, allergic, and other) reactions within 24 hours (none, mild, moderate, and severe), DMT use, and other attributes. Multivariable models characterized associations between clinical factors and reactogenicity.</p><p><strong>Results: </strong>In 719 PwMS, 64% reported experiencing a reaction after their first vaccination shot, and 17% reported a severe reaction. The most common reactions were pain at injection site (54%), fatigue (34%), headache (28%), and malaise (21%). Younger age, being female, prior SARS-CoV-2 infection, and receiving the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) vs BNT162b2 (Pfizer-BioNTech) vaccine were associated with experiencing a reaction after the first vaccine dose. Similar relationships were observed for a severe reaction, including higher odds of reactions among PwMS with more physical impairment and lower odds of reactions for PwMS on an alpha4-integrin blocker or sphingosine-1-phosphate receptor modulator. In 442 PwMS who received their second vaccination shot, 74% reported experiencing a reaction, whereas 22% reported a severe reaction. Reaction profiles after the second shot were similar to those reported after the first shot. Younger PwMS and those who received the mRNA-1273 (Moderna) vs BNT162b2 vaccine reported higher reactogenicity after the second shot, whereas those on a sphingosine-1-phosphate receptor modulator or fumarate were significantly less likely to report a reaction.</p><p><strong>Discussion: </strong>SARS-CoV-2 vaccine reactogenicity profiles and the associated factors in this convenience sample of PwMS appear similar to those reported in the general population. PwMS on specific DMTs were less likely to report vaccine reactions. Overall, the short-term vaccine reactions experienced in the study population were mostly self-limiting, including pain at the injection site, fatigue, headache, and fever.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/25/28/NEURIMMINFL2021039344.PMC8579248.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39857925","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":"CCR5 Blockade in Inflammatory PML and PML-IRIS Associated With Chronic Inflammatory Diseases' Treatments.","authors":"Raphael Bernard-Valnet,&nbsp;Xavier Moisset,&nbsp;Nicolas Maubeuge,&nbsp;Mathilde Lefebvre,&nbsp;Jean-Christophe Ouallet,&nbsp;Mathilde Roumier,&nbsp;Christine Lebrun-Frenay,&nbsp;Jonathan Ciron,&nbsp;Damien Biotti,&nbsp;Pierre Clavelou,&nbsp;Bertrand Godeau,&nbsp;Renaud A Du Pasquier,&nbsp;Guillaume Martin-Blondel","doi":"10.1212/NXI.0000000000001097","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001097","url":null,"abstract":"<p><strong>Background and objectives: </strong>Progressive multifocal leukoencephalopathy (PML) is a disabling neurologic disorder resulting from the infection of the CNS by JC polyomavirus in immunocompromised individuals. For the last 2 decades, increasing use of immunotherapies leads to iatrogenic PML. Iatrogenic PML is often associated with signs of inflammation at onset (inflammatory PML) and/or after treatment withdrawal immune reconstitution inflammatory syndrome (PML-IRIS). Although immune reconstitution is a key element for viral clearance, it may also be harmful and induce clinical worsening. A C-C chemokine receptor type 5 (CCR5) antagonist (maraviroc) has been proposed to prevent and/or limit the deleterious immune responses underlying PML-IRIS. However, the data to support its use remain scarce and disputed.</p><p><strong>Methods: </strong>We conducted a multicenter retrospective cohort study at 8 university hospitals in France and Switzerland by collecting clinical, biological, and radiologic data of patients who developed inflammatory PML (iPML) or PML-IRIS related to immunosuppressive therapies used for chronic inflammatory diseases between 2010 and 2020. We added to this cohort, a meta-analysis of individual case reports of patients with iPML/PML-IRIS treated with maraviroc published up to 2021.</p><p><strong>Results: </strong>Overall, 27 cases were identified in the cohort and 9 from the literature. Among them, 27 met the inclusion criteria: 16 treated with maraviroc and 11 with standard of care (including corticosteroids use). Most cases were related to MS (92.6%) and natalizumab (88%). Inflammatory features (iPML) were present at onset in 12 patients (44.4%), and most patients (92.6%) received corticosteroids within the course of PML. Aggravation due to PML-IRIS was not prevented by maraviroc compared with patients who received only corticosteroids (adjusted odds ratio: 0.408, 95% CI: 0.06-2.63). Similarly, maraviroc did not influence time to clinical worsening due to PML-IRIS (adjusted hazard ratio = 0.529, 95% CI: 0.14-2.0) or disability at the last follow-up (adjusted odds ratio: 2, 95% CI: 0.23-17.3).</p><p><strong>Discussion: </strong>The use of CCR5 blockade did not help to keep deleterious immune reconstitution in check even when associated with corticosteroids. Despite maraviroc's reassuring safety profile, this study does not support its use in iPML/PML-IRIS.</p><p><strong>Classification of evidence: </strong>This study provides Class IV evidence showing that adding maraviroc to the management of iatrogenic iPML/PML-IRIS does not improve the outcome.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39689418","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":"GRP78 Antibodies Are Associated With Blood-Brain Barrier Breakdown in Anti-Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disorder.","authors":"Fumitaka Shimizu,&nbsp;Ryo Ogawa,&nbsp;Yoichi Mizukami,&nbsp;Kenji Watanabe,&nbsp;Kanako Hara,&nbsp;Chihiro Kadono,&nbsp;Toshiyuki Takahashi,&nbsp;Tatsuro Misu,&nbsp;Yukio Takeshita,&nbsp;Yasuteru Sano,&nbsp;Miwako Fujisawa,&nbsp;Toshihiko Maeda,&nbsp;Ichiro Nakashima,&nbsp;Kazuo Fujihara,&nbsp;Takashi Kanda","doi":"10.1212/NXI.0000000000001038","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001038","url":null,"abstract":"<p><strong>Background and objectives: </strong>To analyze (1) the effect of immunoglobulin G (IgG) from patients with anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disorder on the blood-brain barrier (BBB) endothelial cells and (2) the positivity of glucose-regulated protein 78 (GRP78) antibodies in MOG-Ab-associated disorders.</p><p><strong>Methods: </strong>IgG was purified from sera with patients with MOG-Ab-associated disorder in the acute phase (acute MOG, n = 15), in the stable stage (stable MOG, n = 14), healthy controls (HCs, n = 9), and disease controls (DCs, n = 27). Human brain microvascular endothelial cells (BMECs) were incubated with IgG, and the number of nuclear NF-κB p65-positive cells in BMECs using high-content imaging system and the quantitative messenger RNA change in gene expression over the whole transcriptome using RNA-seq were analyzed. GRP78 antibodies from patient IgGs were detected by Western blotting.</p><p><strong>Results: </strong>IgG in the acute MOG group significantly induced the nuclear translocation of NF-κB and increased the vascular cell adhesion molecule 1/intercellular adhesion molecule 1 expression/permeability of 10-kDa dextran compared with that from the stable MOG and HC/DC groups. RNA-seq and pathway analysis revealed that NF-κB signaling and oxidative stress (NQO1) play key roles. The NQO1 and Nrf2 protein amounts were significantly decreased after exposure to IgG in the acute MOG group. The rate of GRP78 antibody positivity in the acute MOG group (10/15, 67% [95% confidence interval, 38%-88%]) was significantly higher than that in the stable MOG group (5/14, 36% [13%-65%]), multiple sclerosis group (4/29, 14% [4%-32%]), the DCs (3/27, 11% [2%-29%]), or HCs (0/9, 0%). Removal of GRP78 antibodies from MOG-IgG reduced the effect on NF-κB nuclear translocation and increased permeability.</p><p><strong>Discussion: </strong>GRP78 antibodies may be associated with BBB dysfunction in MOG-Ab-associated disorder.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ad/d5/NEURIMMINFL2021038608.PMC8561843.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39849133","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":"CNS Involvement in Chronic Inflammatory Demyelinating Polyneuropathy: Subtle Retinal Changes in Optical Coherence Tomography.","authors":"Jens Ingwersen,&nbsp;Jonas Graf,&nbsp;Julia Kluge,&nbsp;Margit Weise,&nbsp;Michael Dietrich,&nbsp;John-Ih Lee,&nbsp;Jens Harmel,&nbsp;Hans-Peter Hartung,&nbsp;Tobias Ruck,&nbsp;Sven G Meuth,&nbsp;Philipp Albrecht,&nbsp;Orhan Aktas,&nbsp;Marius Ringelstein","doi":"10.1212/NXI.0000000000001099","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001099","url":null,"abstract":"<p><strong>Background and objectives: </strong>Chronic inflammatory demyelinating polyneuropathy (CIDP) is an autoimmune disease primarily affecting the peripheral nervous system. However, several noncontrolled studies have suggested concomitant inflammatory CNS demyelination similar to multiple sclerosis. The aim of this study was to investigate an involvement of the visual pathway in patients with CIDP.</p><p><strong>Methods: </strong>In this prospective cross-sectional study, we used high-resolution spectral-domain optical coherence tomography to compare the thickness of the peripapillary retinal nerve fiber layer and the deeper macular retinal layers as well as the total macular volume (TMV) in 22 patients with CIDP and 22 age-matched and sex-matched healthy control (HC) individuals. Retinal layers were semiautomatically segmented by the provided software and were correlated with clinical measures and nerve conduction studies.</p><p><strong>Results: </strong>In patients with CIDP compared with healthy age-matched and sex-matched controls, we found slight but significant volume reductions of the ganglion cell/inner plexiform layer complex (CIDP 1.86 vs HC 1.95 mm³, <i>p</i> = 0.015), the retinal pigment epithelium (CIDP 0.38 vs HC 0.40 mm³, <i>p</i> = 0.02), and the TMV (CIDP 8.48 vs HC 8.75 mm³, <i>p</i> = 0.018). The ganglion cell layer volume and motor nerve conduction velocity were positively associated (B = 0.002, <i>p</i> = 0.02).</p><p><strong>Discussion: </strong>Our data reveal subtle retinal neurodegeneration in patients with CIDP, providing evidence for visual pathway involvement, detectable by OCT. The results need corroboration in independent, larger cohorts.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e4/c1/NEURIMMINFL2021039086.PMC8529418.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39533672","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 Chains in CSF Predict Early Multiple Sclerosis Disease Activity.","authors":"Klaus Berek,&nbsp;Gabriel Bsteh,&nbsp;Michael Auer,&nbsp;Franziska Di Pauli,&nbsp;Astrid Grams,&nbsp;Dejan Milosavljevic,&nbsp;Paulina Poskaite,&nbsp;Christine Schnabl,&nbsp;Sebastian Wurth,&nbsp;Anne Zinganell,&nbsp;Thomas Berger,&nbsp;Janette Walde,&nbsp;Florian Deisenhammer,&nbsp;Harald Hegen","doi":"10.1212/NXI.0000000000001005","DOIUrl":"https://doi.org/10.1212/NXI.0000000000001005","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether κ-free light chain (κ-FLC) index predicts multiple sclerosis (MS) disease activity independent of demographics, clinical characteristics, and MRI findings.</p><p><strong>Methods: </strong>Patients with early MS who had CSF and serum sampling at disease onset were followed for 4 years. At baseline, age, sex, type of symptoms, corticosteroid treatment, and number of T2 hyperintense (T2L) and contrast-enhancing T1 lesions (CELs) on MRI were determined. During follow-up, the occurrence of a second clinical attack and start of disease-modifying therapy (DMT) were registered. κ-FLCs were measured by nephelometry, and κ-FLC index calculated as [CSF κ-FLC/serum κ-FLC]/albumin quotient.</p><p><strong>Results: </strong>A total of 88 patients at a mean age of 33 ± 10 years and female predominance of 68% were included; 38 (43%) patients experienced a second clinical attack during follow-up. In multivariate Cox regression analysis adjusting for age, sex, T2L, CEL, disease and follow-up duration, administration of corticosteroids at baseline and DMT during follow-up revealed that κ-FLC index predicts time to second clinical attack. Patients with κ-FLC index >100 (median value 147) at baseline had a twice as high probability for a second clinical attack within 12 months than patients with low κ-FLC index (median 28); within 24 months, the chance in patients with high κ-FLC index was 4 times as high as in patients with low κ-FLC index. The median time to second attack was 11 months in patients with high κ-FLC index whereas 36 months in those with low κ-FLC index.</p><p><strong>Conclusion: </strong>High κ-FLC index predicts early MS disease activity.</p><p><strong>Classification of evidence: </strong>This study provides Class II evidence that in patients with early MS, high κ-FLC index is an independent risk factor for early second clinical attack.</p>","PeriodicalId":520720,"journal":{"name":"Neurology(R) neuroimmunology & neuroinflammation","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2021-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/96/11/NEURIMMINFL2020036418.PMC8168046.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38960776","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}