Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient
Saxena, Abhishek1,6; Stevens, Jo1; Cetin, Hakan2; Koneczny, Inga1; Webster, Richard2; Lazaridis, Konstantinos3; Tzartos, Socrates3; Vrolix, Kathleen1; Nogales-Gadea, Gisela1,7,8; Machiels, Barbie1; Molenaar, Peter C.1; Damoiseaux, Jan4; De Baets, Marc H.1; Simon-Keller, Katja; Marx, Alexander5; Vincent, Angela2; Losen, Mario1; Martinez-Martinez, Pilar1
2017-10-31
Source PublicationSCIENTIFIC REPORTS
ISSN2045-2322
Volume7
Status已发表
DOI10.1038/s41598-017-14350-8
AbstractWe report here the sequence and functional characterization of a recombinantly expressed autoantibody (mAb 131) previously isolated from a myasthenia gravis patient by immortalization of thymic B cells using Epstein-Barr virus and TLR9 activation. The antibody is characterized by a high degree of somatic mutations as well as a 6 amino acid insertion within the VHCDR2. The recombinant mAb 131 is specific for the.-subunit of the fetal AChR to which it bound with sub-nanomolar apparent affinity, and detected the presence of fetal AChR on a number of rhabdomyosarcoma cell lines. Mab 131 blocked one of the two a-bungarotoxin binding sites on the fetal AChR, and partially blocked the binding of an antibody (mAb 637) to the a-subunit of the AChR, suggesting that both antibodies bind at or near one ACh binding site at the a/gamma subunit interface. However, mAb 131 did not reduce fetal AChR ion channel currents in electrophysiological experiments. These results indicate that mAb 131, although generated from an MG patient, is unlikely to be pathogenic and may make it a potentially useful reagent for studies of myasthenia gravis, rhabdomyosarcoma and arthrogryposis multiplex congenita which can be caused by fetal-specific AChR-blocking autoantibodies.
Indexed BySCI
Language英语
Funding ProjectAustrian Science Fund (FWF)[J3589]
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000414231000027
PublisherNATURE PUBLISHING GROUP
WOS KeywordARTHROGRYPOSIS MULTIPLEX CONGENITA ; NICOTINIC ACETYLCHOLINE-RECEPTOR ; CLASSICAL COMPLEMENT ACTIVATION ; FAB-ARM EXCHANGE ; NEUROMUSCULAR-JUNCTION ; SOMATIC HYPERMUTATION ; FETAL ANTIGEN ; B-CELLS ; THYMUS ; AUTOANTIBODIES
Original Document TypeArticle
Citation statistics
Cited Times:8[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttps://kms.shanghaitech.edu.cn/handle/2MSLDSTB/10020
Collection免疫化学研究所_特聘教授组_抗体工程学实验室
免疫化学研究所_特聘教授组_功能筛选实验室
免疫化学研究所_公共科研平台_抗体筛选平台
Corresponding AuthorLosen, Mario; Martinez-Martinez, Pilar
Affiliation1.Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
2.John Radcliffe Univ Hosp, Nuffield Dept Clin Neurosci, Oxford, England
3.Hellenic Pasteur Inst, 127 Vasilissis Sofias Ave 115 21, Athens, Greece
4.Maastricht Univ, Cent Diagnost Lab, Med Ctr, Maastricht, Netherlands
5.Heidelberg Univ, Univ Med Ctr Mannheim, Inst Pathol, Theodor Kutzer Ufer 1-3, D-68167 Mannheim, Germany
6.ShanghaiTech Univ, Lab Antibody Engn, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China
7.Univ Autonoma Barcelona, Neuromuscular & Neuropediat Dis Res Grp, Inst Invest Ciencies Salut Germans Trias & Pujol, Badalona, Spain
8.Univ Autonoma Barcelona, Campus Can Ruti, Badalona, Spain
First Author AffilicationShanghai Institute for Advanced Immunochemical Studies
Recommended Citation
GB/T 7714
Saxena, Abhishek,Stevens, Jo,Cetin, Hakan,et al. Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient[J]. SCIENTIFIC REPORTS,2017,7.
APA Saxena, Abhishek.,Stevens, Jo.,Cetin, Hakan.,Koneczny, Inga.,Webster, Richard.,...&Martinez-Martinez, Pilar.(2017).Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient.SCIENTIFIC REPORTS,7.
MLA Saxena, Abhishek,et al."Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient".SCIENTIFIC REPORTS 7(2017).
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