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Interleukin-6 Signaling Blockade Induces Regulatory Plasmablasts in Neuromyelitis Optica Spectrum Disorder. 白细胞介素-6 信号传导阻断诱导神经脊髓炎视网膜频谱紊乱症中的调节性浆细胞
IF 7.8 1区 医学
Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-07-01 Epub Date: 2024-06-18 DOI: 10.1212/NXI.0000000000200266
Ritsu Akatani, Norio Chihara, Atsushi Hara, Asato Tsuji, Shusuke Koto, Kazuhiro Kobayashi, Tatsushi Toda, Riki Matsumoto
{"title":"Interleukin-6 Signaling Blockade Induces Regulatory Plasmablasts in Neuromyelitis Optica Spectrum Disorder.","authors":"Ritsu Akatani, Norio Chihara, Atsushi Hara, Asato Tsuji, Shusuke Koto, Kazuhiro Kobayashi, Tatsushi Toda, Riki Matsumoto","doi":"10.1212/NXI.0000000000200266","DOIUrl":"10.1212/NXI.0000000000200266","url":null,"abstract":"<p><strong>Background and objectives: </strong>Interleukin-6 receptor antibodies (IL-6R Abs), including satralizumab, are increasingly used to prevent relapse for neuromyelitis optica spectrum disorder (NMOSD). However, the detailed mechanism of action of this treatment on the lymphocyte phenotype remains unclear. This study focused on B cells in patients with NMOSD, hypothesizing that IL-6R Ab enables B cells to acquire regulatory functions by producing the anti-inflammatory cytokine IL-10.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cells were stimulated in vitro to induce the expansion of B-cell subsets, double-negative B cells (DNs; CD19<sup>+</sup> IgD<sup>-</sup>, CD27<sup>-</sup>) and plasmablasts (PBs; CD19<sup>+</sup>, CD27<sup>hi</sup>, CD38<sup>hi</sup>). Whole B cells, DNs, or PBs were isolated after culture with IL-6R Ab, and IL-10 expression was quantified using quantitative PCR and a cytometric bead array. RNA sequencing was performed to identify the marker of regulatory PBs induced by IL-6R Ab.</p><p><strong>Results: </strong>DNs and PBs were observed to expand in patients with NMSOD during the acute attacks. In the in vitro model, IL-6R Ab increased IL-10 expression in B cells. Notably, IL-10 expression increased in PBs but not in DNs. Using RNA sequencing, CD200 was identified as a marker of regulatory PBs among the differentially expressed upregulated genes. CD200<sup>+</sup> PBs produced more IL-10 than CD200<sup>-</sup> PBs. Furthermore, patients with NMOSD who received satralizumab had a higher proportion of CD200<sup>+</sup> PBs than patients during the acute attacks.</p><p><strong>Discussion: </strong>Treatment with IL-6 signaling blockade elicited a regulatory phenotype in B cells and PBs. CD200<sup>+</sup> PBs may be a marker of treatment responsiveness in the context of NMOSD pathophysiology.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200266"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11188987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420053","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}
引用次数: 0
Advancing Knowledge in CNS Vasculitis. 增进对中枢神经系统血管炎的了解。
IF 7.8 1区 医学
Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-07-01 Epub Date: 2024-06-10 DOI: 10.1212/NXI.0000000000200272
Christian Pagnoux, Hubert de Boysson
{"title":"Advancing Knowledge in CNS Vasculitis.","authors":"Christian Pagnoux, Hubert de Boysson","doi":"10.1212/NXI.0000000000200272","DOIUrl":"10.1212/NXI.0000000000200272","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200272"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11194713/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141301108","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}
引用次数: 0
Neonatal B-Cell Levels and Infant Health in Newborns Potentially Exposed to Anti-CD20 Monoclonal Antibodies During Pregnancy or Lactation. 妊娠期或哺乳期可能接触抗CD20单克隆抗体的新生儿B细胞水平和婴儿健康。
IF 7.8 1区 医学
Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-07-01 Epub Date: 2024-06-13 DOI: 10.1212/NXI.0000000000200264
Carolin Schwake, Julia Steinle, Sandra Thiel, Nina Timmesfeld, Sabrina Haben, Ilya Ayzenberg, Ralf Gold, Kerstin Hellwig
{"title":"Neonatal B-Cell Levels and Infant Health in Newborns Potentially Exposed to Anti-CD20 Monoclonal Antibodies During Pregnancy or Lactation.","authors":"Carolin Schwake, Julia Steinle, Sandra Thiel, Nina Timmesfeld, Sabrina Haben, Ilya Ayzenberg, Ralf Gold, Kerstin Hellwig","doi":"10.1212/NXI.0000000000200264","DOIUrl":"10.1212/NXI.0000000000200264","url":null,"abstract":"<p><strong>Objectives: </strong>To report CD19<sup>+</sup> B-cell counts and possible adverse effects on infants of mothers exposed to anti-CD20 mAbs ≤6 months before/during pregnancy or lactation.</p><p><strong>Methods: </strong>We conducted a retrospective study using data from the German nationwide neuroimmunologic pregnancy registry. Inclusion criteria involved infants whose mothers received anti-CD20 mAbs ≤6 months before/during pregnancy or lactation, with ≥1 postnatal CD19<sup>+</sup> B-cell count. Main outcomes were absolute and relative CD19<sup>+</sup> B-cell counts. Comparison with reference values was performed conservatively in a subgroup with maternal exposure ≤3 months before/during pregnancy. Additional outcomes included pregnancy results, severe infections, and lymphocyte counts.</p><p><strong>Results: </strong>The cohort comprised 49 infants (F:M 25:24) exposed to anti-CD20 mAbs ≤6 months before/during pregnancy or lactation. CD19<sup>+</sup> B-cell and lymphocyte counts in 40 infants with maternal exposure ≤3 months before/during pregnancy were comparable with normative values. Only 2 cases of complete CD19<sup>+</sup> B-cell depletion occurred after second-trimester and third-trimester ocrelizumab exposure, with repopulation observed within 2 months. Exclusive lactation exposure had no significant effect on infants' absolute CD19<sup>+</sup> B-cell counts.</p><p><strong>Discussion: </strong>Administering anti-CD20 mAbs before or at the pregnancy onset, or during lactation, seems safe without significant impact on infant B-cell development. However, second-trimester or third-trimester exposure can cause CD19<sup>+</sup> B-cell depletion due to placental transfer, necessitating monitoring and postponing live vaccines.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200264"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11178251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141317893","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}
引用次数: 0
Ocrelizumab Alters Cytotoxic Lymphocyte Function While Reducing EBV-Specific CD8+ T-Cell Proliferation in Patients With Multiple Sclerosis. 奥克雷珠单抗可改变多发性硬化症患者的细胞毒性淋巴细胞功能,同时减少 EBV 特异性 CD8+ T 细胞增殖
IF 8.8 1区 医学
Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-07-01 Epub Date: 2024-04-25 DOI: 10.1212/NXI.0000000000200250
Gianmarco Abbadessa, Maria Teresa Lepore, Sara Bruzzaniti, Erica Piemonte, Giuseppina Miele, Elisabetta Signoriello, Francesco Perna, Chiara De Falco, G Lus, Giuseppe Matarese, Simona Bonavita, Mario Galgani
{"title":"Ocrelizumab Alters Cytotoxic Lymphocyte Function While Reducing EBV-Specific CD8<sup>+</sup> T-Cell Proliferation in Patients With Multiple Sclerosis.","authors":"Gianmarco Abbadessa, Maria Teresa Lepore, Sara Bruzzaniti, Erica Piemonte, Giuseppina Miele, Elisabetta Signoriello, Francesco Perna, Chiara De Falco, G Lus, Giuseppe Matarese, Simona Bonavita, Mario Galgani","doi":"10.1212/NXI.0000000000200250","DOIUrl":"10.1212/NXI.0000000000200250","url":null,"abstract":"<p><strong>Background and objectives: </strong>The role of B cells in the pathogenic events leading to relapsing multiple sclerosis (R-MS) has only been recently elucidated. A pivotal step in defining this role has been provided by therapeutic efficacy of anti-CD20 monoclonal antibodies. Indeed, treatment with anti-CD20 can also alter number and function of other immune cells not directly expressing CD20 on their cell surface, whose activities can contribute to unknown aspects influencing therapeutic efficacy. We examined the phenotype and function of cytotoxic lymphocytes and Epstein-Barr virus (EBV)-specific immune responses in people with R-MS before and after ocrelizumab treatment.</p><p><strong>Methods: </strong>In this prospective study, we collected blood samples from people with R-MS (n = 41) before and 6 and 12 months after initiating ocrelizumab to assess the immune phenotype and the indirect impact on cytotoxic functions of CD8<sup>+</sup> T and NK cells. In addition, we evaluated the specific anti-EBV proliferative responses of both CD8<sup>+</sup> T and NK lymphocytes as surrogate markers of anti-EBV activity.</p><p><strong>Results: </strong>We observed that while ocrelizumab depleted circulating B cells, it also reduced the expression of activation and migratory markers on both CD8<sup>+</sup> T and NK cells as well as their in vitro cytotoxic activity. A comparable pattern in the modulation of immune molecules by ocrelizumab was observed in cytotoxic cells even when patients with R-MS were divided into groups based on their prior disease-modifying treatment. These effects were accompanied by a significant and selective reduction of CD8<sup>+</sup> T-cell proliferation in response to EBV antigenic peptides.</p><p><strong>Discussion: </strong>Taken together, our findings suggest that ocrelizumab-while depleting B cells-affects the cytotoxic function of CD8<sup>+</sup> and NK cells, whose reduced cross-activity against myelin antigens might also contribute to its therapeutic efficacy during MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200250"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850873","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}
引用次数: 0
Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis. 用于多发性硬化症诊断和预后检查的中央静脉征、皮质病变和顺磁边缘病变。
IF 7.8 1区 医学
Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-07-01 Epub Date: 2024-05-24 DOI: 10.1212/NXI.0000000000200253
Serena Borrelli, Maria Sofia Martire, Anna Stölting, Colin Vanden Bulcke, Edoardo Pedrini, François Guisset, Céline Bugli, Halil Yildiz, Lucie Pothen, Sophie Elands, Vittorio Martinelli, Bryan Smith, Steven Jacobson, Renaud A Du Pasquier, Vincent Van Pesch, Massimo Filippi, Daniel S Reich, Martina Absinta, Pietro Maggi
{"title":"Central Vein Sign, Cortical Lesions, and Paramagnetic Rim Lesions for the Diagnostic and Prognostic Workup of Multiple Sclerosis.","authors":"Serena Borrelli, Maria Sofia Martire, Anna Stölting, Colin Vanden Bulcke, Edoardo Pedrini, François Guisset, Céline Bugli, Halil Yildiz, Lucie Pothen, Sophie Elands, Vittorio Martinelli, Bryan Smith, Steven Jacobson, Renaud A Du Pasquier, Vincent Van Pesch, Massimo Filippi, Daniel S Reich, Martina Absinta, Pietro Maggi","doi":"10.1212/NXI.0000000000200253","DOIUrl":"10.1212/NXI.0000000000200253","url":null,"abstract":"<p><strong>Background and objectives: </strong>The diagnosis of multiple sclerosis (MS) can be challenging in clinical practice because MS presentation can be atypical and mimicked by other diseases. We evaluated the diagnostic performance, alone or in combination, of the central vein sign (CVS), paramagnetic rim lesion (PRL), and cortical lesion (CL), as well as their association with clinical outcomes.</p><p><strong>Methods: </strong>In this multicenter observational study, we first conducted a cross-sectional analysis of the CVS (proportion of CVS-positive lesions or simplified determination of CVS in 3/6 lesions-Select3*/Select6*), PRL, and CL in MS and non-MS cases on 3T-MRI brain images, including 3D T2-FLAIR, T2*-echo-planar imaging magnitude and phase, double inversion recovery, and magnetization prepared rapid gradient echo image sequences. Then, we longitudinally analyzed the progression independent of relapse and MRI activity (PIRA) in MS cases over the 2 years after study entry. Receiver operating characteristic curves were used to test diagnostic performance and regression models to predict diagnosis and clinical outcomes.</p><p><strong>Results: </strong>The presence of ≥41% CVS-positive lesions/≥1 CL/≥1 PRL (optimal cutoffs) had 96%/90%/93% specificity, 97%/84%/60% sensitivity, and 0.99/0.90/0.77 area under the curve (AUC), respectively, to distinguish MS (n = 185) from non-MS (n = 100) cases. The Select3*/Select6* algorithms showed 93%/95% specificity, 97%/89% sensitivity, and 0.95/0.92 AUC. The combination of CVS, CL, and PRL improved the diagnostic performance, especially when Select3*/Select6* were used (93%/94% specificity, 98%/96% sensitivity, 0.99/0.98 AUC; <i>p</i> = 0.002/<i>p</i> < 0.001). In MS cases (n = 185), both CL and PRL were associated with higher MS disability and severity. Longitudinal analysis (n = 61) showed that MS cases with >4 PRL at baseline were more likely to experience PIRA at 2-year follow-up (odds ratio 17.0, 95% confidence interval: 2.1-138.5; <i>p</i> = 0.008), whereas no association was observed between other baseline MRI measures and PIRA, including the number of CL.</p><p><strong>Discussion: </strong>The combination of CVS, CL, and PRL can improve MS differential diagnosis. CL and PRL also correlated with clinical measures of poor prognosis, with PRL being a predictor of disability accrual independent of clinical/MRI activity.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200253"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11129678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141094083","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}
引用次数: 0
Corrections to Preprint Server Information. 预印本服务器信息更正。
IF 7.8 1区 医学
Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-07-01 Epub Date: 2024-05-16 DOI: 10.1212/NXI.0000000000200267
{"title":"Corrections to Preprint Server Information.","authors":"","doi":"10.1212/NXI.0000000000200267","DOIUrl":"10.1212/NXI.0000000000200267","url":null,"abstract":"","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200267"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11195433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956839","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}
引用次数: 0
Alterations of Thymus-Derived Tregs in Multiple Sclerosis. 多发性硬化症胸腺衍生集落的变化
IF 8.8 1区 医学
Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-07-01 Epub Date: 2024-06-04 DOI: 10.1212/NXI.0000000000200251
Tiziana Lorenzini, Wolfgang Faigle, Josefine Ruder, María José Docampo, Lennart Opitz, Roland Martin
{"title":"Alterations of Thymus-Derived Tregs in Multiple Sclerosis.","authors":"Tiziana Lorenzini, Wolfgang Faigle, Josefine Ruder, María José Docampo, Lennart Opitz, Roland Martin","doi":"10.1212/NXI.0000000000200251","DOIUrl":"10.1212/NXI.0000000000200251","url":null,"abstract":"<p><strong>Background and objectives: </strong>Multiple sclerosis (MS) is considered a prototypic autoimmune disease of the CNS. It is the leading cause of chronic neurologic disability in young adults. Proinflammatory B cells and autoreactive T cells both play important roles in its pathogenesis. We aimed to study alterations of regulatory T cells (Tregs), which likely also contribute to the disease, but their involvement is less clear.</p><p><strong>Methods: </strong>By combining multiple experimental approaches, we examined the Treg compartments in 41 patients with relapsing-remitting MS and 17 healthy donors.</p><p><strong>Results: </strong>Patients with MS showed a reduced frequency of CD4<sup>+</sup> T cells and Foxp3+ Tregs and age-dependent alterations of Treg subsets. Treg suppressive function was compromised in patients, who were treated with natalizumab, while it was unaffected in untreated and anti-CD20-treated patients. The changes in natalizumab-treated patients included increased proinflammatory cytokines and an altered transcriptome in thymus-derived (t)-Tregs, but not in peripheral (p)-Tregs.</p><p><strong>Discussion: </strong>Treg dysfunction in patients with MS might be related to an altered transcriptome of t-Tregs and a proinflammatory environment. Our findings contribute to a better understanding of Tregs and their subtypes in MS.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200251"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11160584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262317","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}
引用次数: 0
Positive Allosteric Modulation of NMDARs Prevents the Altered Surface Dynamics Caused by Patients' Antibodies. 对 NMDARs 的正向异构调节可防止患者抗体引起的表面动力学改变。
IF 8.8 1区 医学
Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-07-01 Epub Date: 2024-05-21 DOI: 10.1212/NXI.0000000000200261
Estibaliz Maudes, Zoë Jamet, Laura Marmolejo, Josep O Dalmau, Laurent Groc
{"title":"Positive Allosteric Modulation of NMDARs Prevents the Altered Surface Dynamics Caused by Patients' Antibodies.","authors":"Estibaliz Maudes, Zoë Jamet, Laura Marmolejo, Josep O Dalmau, Laurent Groc","doi":"10.1212/NXI.0000000000200261","DOIUrl":"10.1212/NXI.0000000000200261","url":null,"abstract":"<p><strong>Objectives: </strong>A positive allosteric modulator of the NMDAR, SGE-301, has been shown to reverse the alterations caused by the antibodies of patients with anti-NMDAR encephalitis (NMDARe). However, the mechanisms involved beyond receptor modulation are unclear. In this study, we aimed to investigate how this modulator affects NMDAR membrane dynamics.</p><p><strong>Methods: </strong>Cultured hippocampal neurons were treated with SGE-301 or vehicle, alongside with immunoglobulins G (IgG) from patients with NMDARe or healthy controls. NMDAR surface dynamics were assessed with single-molecule imaging by photoactivated localization microscopy.</p><p><strong>Results: </strong>NMDAR trajectories from neurons treated with SGE-301 were less confinement, with increased diffusion coefficients. This effect mainly occurred at synapses because extrasynaptic diffusion and confinement were minimally affected by SGE-301. Treatment with patients' IgG reduced NMDAR surface dynamics and increased their confinement. Remarkably, SGE-301 incubation antagonized patients' IgG effects in both synaptic and extrasynaptic membrane compartments, restoring diffusion and confinement values similar to those from neurons exposed to control IgG.</p><p><strong>Discussion: </strong>We demonstrate that SGE-301 upregulates NMDAR surface diffusion and antagonizes the pathogenic effects of patients' IgG on NMDAR membrane organization. These findings suggest a potential therapeutic strategy for NMDARe.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200261"},"PeriodicalIF":8.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11111324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141076381","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}
引用次数: 0
Serum Proteomics Distinguish Subtypes of NMO Spectrum Disorder and MOG Antibody-Associated Disease and Highlight Effects of B-Cell Depletion. 血清蛋白质组学可区分 NMO 谱系障碍和 MOG 抗体相关疾病的亚型,并突出 B 细胞耗竭的影响。
IF 7.8 1区 医学
Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-07-01 Epub Date: 2024-06-17 DOI: 10.1212/NXI.0000000000200268
Saurabh Gawde, Nadja Siebert, Klemens Ruprecht, Gaurav Kumar, Rose M Ko, Kaylea Massey, Joel M Guthridge, Yang Mao-Draayer, Patrick Schindler, Maria Hastermann, Gabriel Pardo, Friedemann Paul, Robert C Axtell
{"title":"Serum Proteomics Distinguish Subtypes of NMO Spectrum Disorder and MOG Antibody-Associated Disease and Highlight Effects of B-Cell Depletion.","authors":"Saurabh Gawde, Nadja Siebert, Klemens Ruprecht, Gaurav Kumar, Rose M Ko, Kaylea Massey, Joel M Guthridge, Yang Mao-Draayer, Patrick Schindler, Maria Hastermann, Gabriel Pardo, Friedemann Paul, Robert C Axtell","doi":"10.1212/NXI.0000000000200268","DOIUrl":"10.1212/NXI.0000000000200268","url":null,"abstract":"<p><strong>Background and objectives: </strong>AQP4 antibody-positive NMOSD (AQP4-NMOSD), MOG antibody-associated disease (MOGAD), and seronegative NMOSD (SN-NMOSD) are neuroautoimmune conditions that have overlapping clinical manifestations. Yet, important differences exist in these diseases, particularly in B-cell depletion (BCD) efficacy. Yet, the biology driving these differences remains unclear. Our study aims to clarify biological pathways distinguishing these diseases beyond autoantibodies and investigate variable BCD effects through proteomic comparisons.</p><p><strong>Methods: </strong>In a retrospective study, 1,463 serum proteins were measured in 53 AQP4-NMOSD, 25 MOGAD, 18 SN-NMOSD, and 49 healthy individuals. To identify disease subtype-associated signatures, we examined serum proteins in patients without anti-CD20 B-cell depletion (NoBCD). We then assessed the effect of BCD treatment within each subtype by comparing proteins between BCD-treated and NoBCD-treated patients.</p><p><strong>Results: </strong>In NoBCD-treated patients, serum profiles distinguished the 3 diseases. AQP4-NMOSD showed elevated type I interferon-induced chemokines (CXCL9 and CXCL10) and TFH chemokine (CXCL13). MOGAD exhibited increased cytotoxic T-cell proteases (granzyme B and granzyme H), while SN-NMOSD displayed elevated Wnt inhibitory factor 1, a marker for nerve injury. Across all subtypes, BCD-treated patients showed reduction of B-cell-associated proteins. In AQP4-NMOSD, BCD led to a decrease in several inflammatory pathways, including IL-17 signaling, cytokine storm, and macrophage activation. By contrast, BCD elevated these pathways in patients with MOGAD. BCD had no effect on these pathways in SN-NMOSD.</p><p><strong>Discussion: </strong>Proteomic profiles show unique biological pathways that distinguish AQP4-NMOSD, MOGAD, or SN-NMOSD. Furthermore, BCD uniquely affects inflammatory pathways in each disease type, providing an explanation for the disparate therapeutic response in AQP4-NMOSD and MOGAD.</p>","PeriodicalId":19472,"journal":{"name":"Neurology® Neuroimmunology & Neuroinflammation","volume":"11 4","pages":"e200268"},"PeriodicalIF":7.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11186702/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141420151","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}
引用次数: 0
Clinical Characterization and Ancillary Tests in Susac Syndrome: A Systematic Review. 苏萨克综合征的临床特征和辅助检查:系统回顾
IF 7.8 1区 医学
Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2024-05-01 Epub Date: 2024-02-16 DOI: 10.1212/NXI.0000000000200209
Adi Wilf-Yarkoni, Ofir Zmira, Assaf Tolkovsky, Barak Pflantzer, Shany G Gofrit, Ilka Kleffner, Friedemann Paul, Jan Dörr
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