与抗髓鞘少突胶质细胞糖蛋白抗体相比,抗水通道蛋白-4更有效地激活补体。

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
{"title":"与抗髓鞘少突胶质细胞糖蛋白抗体相比,抗水通道蛋白-4更有效地激活补体。","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":null,"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<sub>1-3</sub>β<sub>1-3</sub>) 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<sub>1-3</sub>β<sub>1-3</sub>) could induce at least some CDC; however, the strongest MOG-IgG-induced CDC levels were found on MOGα<sub>1</sub>, MOGα<sub>3</sub>, and MOGβ<sub>1</sub>. 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 MOGα<sub>1</sub> and MOGβ<sub>1</sub>. 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":0.0000,"publicationDate":"2022-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682624/pdf/","citationCount":"0","resultStr":"{\"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\":null,\"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<sub>1-3</sub>β<sub>1-3</sub>) 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<sub>1-3</sub>β<sub>1-3</sub>) could induce at least some CDC; however, the strongest MOG-IgG-induced CDC levels were found on MOGα<sub>1</sub>, MOGα<sub>3</sub>, and MOGβ<sub>1</sub>. 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 MOGα<sub>1</sub> and MOGβ<sub>1</sub>. 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\":0.0000,\"publicationDate\":\"2022-11-22\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9682624/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurology(R) neuroimmunology & neuroinflammation\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1212/NXI.0000000000200059\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/1/1 0:00:00\",\"PubModel\":\"Print\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurology(R) neuroimmunology & neuroinflammation","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1212/NXI.0000000000200059","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/1/1 0:00:00","PubModel":"Print","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

背景与目的:研究免疫球蛋白G (IgG)抗水通道蛋白-4抗体(AQP4-IgG)和抗髓鞘少突胶质细胞糖蛋白抗体(MOG-IgG)对罕见脱髓鞘性中枢神经系统视神经脊髓炎谱系障碍(NMOSD)和MOG-IgG相关疾病(MOGAD)患者血清样本补体介导的细胞毒性。方法:用表达不同MOG亚型(MOGα1-3 - β1-3)或AQP4-M23的HEK293A细胞进行细胞检测。细胞与人MOG-IgG或aqp4 - igg阳性血清样品以及活性或热灭活的人补体一起孵育,并用乳酸脱氢酶测定补体依赖性细胞毒性(CDC)。为了进一步量化抗体介导的细胞损伤,流式细胞术分析了末端补体复合物(TCC)的形成。此外,对TCC和补体成分3 (C3)进行免疫细胞化学检测。结果:aqp4 - igg阳性血清的CDC和TCC水平高于mog - igg阳性血清。值得注意的是,两者都显示抗体滴度与CDC以及滴度与TCC水平之间存在相关性。此外,所有6种MOG亚型(MOGα1-3β1-3)均可诱导部分疾病预防控制(CDC);而mog - igg诱导的CDC水平在mog - α1、mog - α3和mog - β1中最高。研究了MOG- igg识别不同MOG亚型的结合模式,发现识别所有6种亚型的MOG- igg再次诱导最高的MOGα1和MOGβ1的CDC水平。此外,TCC和C3的表面染色显示,所有6种MOG亚型以及AQP4-M23均呈阳性。讨论:MOG-IgG和AQP4-IgG均能诱导CDC,并呈滴度依赖性。而AQP4-IgG在体外靶细胞上的CDC水平明显高于MOG。这进一步强调了补体在aqp4 - igg介导的疾病中的作用,并降低了补体激活在mog - igg介导的自身免疫性疾病中的重要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

More Efficient Complement Activation by Anti-Aquaporin-4 Compared With Anti-Myelin Oligodendrocyte Glycoprotein Antibodies.

More Efficient Complement Activation by Anti-Aquaporin-4 Compared With Anti-Myelin Oligodendrocyte Glycoprotein Antibodies.

More Efficient Complement Activation by Anti-Aquaporin-4 Compared With Anti-Myelin Oligodendrocyte Glycoprotein Antibodies.

More Efficient Complement Activation by Anti-Aquaporin-4 Compared With Anti-Myelin Oligodendrocyte Glycoprotein Antibodies.

Background and objectives: 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).

Methods: A cell-based assay with HEK293A cells expressing different MOG isoforms (MOGα1-3β1-3) 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.

Results: 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 (MOGα1-3β1-3) 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.

Discussion: 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.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信