Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient

doi:10.1038/s41598-017-14350-8

KMS > 免疫化学研究所 > 特聘教授组 > Sachdev S.Sidhu组

	Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient
	Saxena, Abhishek1,6 ; Stevens, Jo 1; Cetin, Hakan 2; Koneczny, Inga 1; Webster, Richard 2; Lazaridis, Konstantinos 3; Tzartos, Socrates 3; Vrolix, Kathleen 1; Nogales-Gadea, Gisela 1,7,8; Machiels, Barbie 1; Molenaar, Peter C.1; Damoiseaux, Jan 4; De Baets, Marc H.1; Simon-Keller, Katja ; Marx, Alexander 5; Vincent, Angela 2; Losen, Mario 1; Martinez-Martinez, Pilar 1
	2017-10-31
发表期刊	SCIENTIFIC REPORTS
ISSN	2045-2322
卷号	7
发表状态	已发表
DOI	10.1038/s41598-017-14350-8
摘要	We 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.
收录类别	SCI
语种	英语
资助项目	Austrian Science Fund (FWF)[J3589]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000414231000027
出版者	NATURE PUBLISHING GROUP
WOS关键词	ARTHROGRYPOSIS MULTIPLEX CONGENITA ; NICOTINIC ACETYLCHOLINE-RECEPTOR ; CLASSICAL COMPLEMENT ACTIVATION ; FAB-ARM EXCHANGE ; NEUROMUSCULAR-JUNCTION ; SOMATIC HYPERMUTATION ; FETAL ANTIGEN ; B-CELLS ; THYMUS ; AUTOANTIBODIES
原始文献类型	Article
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/10020
专题	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
通讯作者	Losen, Mario; Martinez-Martinez, Pilar
作者单位	1.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
第一作者单位	免疫化学研究所
推荐引用方式 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).