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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/16341

Title: Clonal heterogeneity of thymic B cells from early-onset myasthenia gravis patients with antibodies against the acetylcholine receptor
Authors: Vrolix, Kathleen
FRAUSSEN, Judith
Losen, Mario
Stevens, Jo
Molenaar, Peter C.
SOMERS, Veerle
Bracho, Maria Alma
Le Panse, Rozen
STINISSEN, Piet
Berrih-Aknin, Sonia
Maessen, Jos G.
Van Garsse, Leen
Buurman, Wim A.
Tzartos, Socrates J.
De Baets, Marc H.
Martinez-Martinez, Pilar
Lazaridis, Konstantinos
Issue Date: 2014
Citation: JOURNAL OF AUTOIMMUNITY, 52, p. 101-112
Abstract: Myasthenia gravis (MG) with antibodies against the acetylcholine receptor (AChR-MG) is considered as a prototypic autoimmune disease. The thymus is important in the pathophysiology of the disease since thymus hyperplasia is a characteristic of early-onset AChR-MG and patients often improve after thymectomy. We hypothesized that thymic B cell and antibody repertoires of AChR-MG patients differ intrinsically from those of control individuals. Using immortalization with Epstein-Barr Virus and Toll-like receptor 9 activation, we isolated and characterized monoclonal B cell lines from 5 MG patients and 8 controls. Only 2 of 570 immortalized B cell clones from MG patients produced antibodies against the AChR (both clones were from the same patient), suggesting that AChR-specific B cells are not enriched in the thymus. Surprisingly, many B cell lines from both AChR-MG and control thymus samples displayed reactivity against striated muscle proteins. Striational antibodies were produced by 15% of B cell clones from AChR-MG versus 6% in control thymus. The IgVH gene sequence analysis showed remarkable similarities, concerning VH family gene distribution, mutation frequency and CDR3 composition, between B cells of AChR-MG patients and controls. MG patients showed clear evidence of clonal B cell expansion in contrast to controls. In this latter aspect, MG resembles multiple sclerosis and clinically isolated syndrome, but differs from systemic lupus erythematosus. Our results support an antigen driven immune response in the MG thymus, but the paucity of AChR-specific B cells, in combination with the observed polyclonal expansions suggest a more diverse immune response than expected.
Notes: Martinez-Martinez, P (reprint author), Maastricht Univ, Fac Hlth Med & Life Sci, Sch Mental Hlth & Neurosci, Dept Neurosci, Universitetssingel 50,POB 616, NL-6200 MD Maastricht, Netherlands. p.martinez@maastrichtuniversity.nl
URI: http://hdl.handle.net/1942/16341
DOI: 10.1016/j.jaut.2013.12.008
ISI #: 000340303500009
ISSN: 0896-8411
Category: A1
Type: Journal Contribution
Validation: ecoom, 2015
Appears in Collections: Research publications

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