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 (John Radcliffe Hospital (Oxford, Regne Unit))
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 (John Radcliffe Hospital (Oxford, Regne Unit))
Vincent, Angela (John Radcliffe Hospital (Oxford, Regne Unit))
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

Data:	2016
Resum:	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.
Ajuts:	Instituto de Salud Carlos III JR13-0001
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:	Annals of Clinical and Translational Neurology, Vol. 3, Issue 6 (June 2016) , p. 443-454, ISSN 2328-9503

DOI: 10.1002/acn3.311
PMID: 27547772

12 p, 385.6 KB

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