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Compromised fidelity of B‐cell tolerance checkpoints in AChR and MuSK myasthenia gravis
Lee, Jae‐Yun (Yale School of Medicine. Department of Neurology)
Stathopoulos, Panos (Yale School of Medicine. Department of Neurology)
Gupta, Sasha (Yale School of Medicine. Department of Neurology)
Bannock, Jason M. (Yale School of Medicine. Department of Immunobiology)
Barohn, Richard J. (University of Kansas Medical Center. Department of Neurology)
Cotzomi, Elizabeth (Yale School of Medicine. Department of Neurology)
Dimachkie, Mazen M. (University of Kansas Medical Center. Department of Neurology)
Jacobson, Leslie (University of Oxford. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital)
Lee, Casey S. (Yale School of Medicine. Department of Neurology)
Morbach, Henner (Yale School of Medicine. Department of Immunobiology)
Querol, Luis (Institut d'Investigació Biomèdica Sant Pau)
Shan, Jing‐Li (Yale School of Medicine. Department of Neurology)
Vander Heiden, Jason A. (Yale University. Interdepartmental Program in Computational Biology and Bioinformatics)
Waters, Patrick (University of Oxford. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital)
Vincent, Angela (University of Oxford. Nuffield Department of Clinical Neurosciences, John Radcliffe Hospital)
Nowak, Richard J. (Yale School of Medicine. Department of Neurology)
O'Connor, Kevin C. (Yale School of Medicine. Department of Neurology)
Universitat Autònoma de Barcelona

Date: 2016
Abstract: Myasthenia gravis () is an autoimmune condition in which neurotransmission is impaired by binding of autoantibodies to acetylcholine receptors (hR) or, in a minority of patients, to muscle specific kinase (Mu). There are differences in the dominant IgG subclass, pathogenic mechanisms, and treatment responses between the two subtypes (hR or Mu). The antibodies are thought to be T‐cell dependent, but the mechanisms underlying their production are not well understood. One aspect not previously described is whether defects in central and peripheral tolerance checkpoints, which allow autoreactive B cells to accumulate in the naive repertoire, are found in both or either form of . An established set of assays that measure the frequency of both polyreactive and autoreactive B cell receptors () in naive populations was applied to specimens collected from patients with either hR or Mu and healthy controls. Radioimmuno‐ and cell‐based assays were used to measure binding to hR and Mu. The frequency of polyreactive and autoreactive s (n = 262) was higher in both hR and Mu patients than in healthy controls. None of the ‐derived s bound hR or Mu. The results indicate that both these subtypes harbor defects in central and peripheral B cell tolerance checkpoints. Defective B cell tolerance may represent a fundamental contributor to autoimmunity in and is of particular importance when considering the durability of myasthenia gravis treatment strategies, particularly biologics that eliminate B cells.
Note: Número d'acord de subvenció ISCIII/JR13-0001
Rights: 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. Creative Commons
Language: Anglès.
Document: article ; publishedVersion
Published in: Annals of Clinical and Translational Neurology, Vol. 3, Issue 6 (June 2016) , p. 443-454, ISSN 2328-9503

PMID: 27547772
DOI: 10.1002/acn3.311


12 p, 385.6 KB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (scientific output) > Health sciences and biosciences > Institut d'Investigació Biomèdica Sant Pau
Articles > Published articles

 Record created 2018-02-07, last modified 2019-09-26



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