Characterization of an anti-fetal AChR monoclonal antibody isolated from a myasthenia gravis patient
Saxena, Abhishek (Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University)
Stevens, Jo (Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University)
Cetin, Hakan (John Radcliffe Hospital (Oxford, Regne Unit))
Koneczny, Inga (Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University)
Webster, Richard (John Radcliffe Hospital (Oxford, Regne Unit))
Lazaridis, Konstantinos (Hellenic Pasteur Institute)
Tzartos, Socrates (Hellenic Pasteur Institute)
Vrolix, Kathleen (Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University)
Nogales, Gisela (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Machiels, Barbie (Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University)
Molenaar, Peter C. (Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University)
Damoiseaux, Jan (Central Diagnostic Laboratory, Maastricht University Medical Center)
De Baets, Marc H. (Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University)
Simon-Keller, Katja (Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg)
Marx, Alexander (Institute of Pathology, University Medical Centre Mannheim, University of Heidelberg)
Vincent, Angela (John Radcliffe Hospital (Oxford, Regne Unit))
Losen, Mario (Maastricht University. Department of Psychiatry and Neuropsychology)
Martinez-Martinez, Pilar (Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht University)
Universitat Autònoma de Barcelona

Data:	2017
Resum:	We report here the sequence and functional characterization of a recombinantly expressed.
Resum:	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 γ-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 α-bungarotoxin binding sites on the fetal AChR, and partially blocked the binding of an antibody (mAb 637) to the α-subunit of the AChR, suggesting that both antibodies bind at or near one ACh binding site at the α/γ 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.
Ajuts:	Instituto de Salud Carlos III CP14/00032 Instituto de Salud Carlos III PI15/01756
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Scientific reports, Vol. 7 (october 2017) , p. 1-12, ISSN 2045-2322

DOI: 10.1038/s41598-017-14350-8
PMID: 29089519

12 p, 5.0 MB

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