Relative frequencies of muscle specific kinase antibody myasthenia in 46 centres worldwide
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ID: 318452
2026
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Abstract
Serum antibodies to muscle specific kinase (MuSK) are present in a proportion of patients with acetylcholine receptor antibody seronegative myasthenia gravis (SNMG), but their reported frequencies in different populations vary. From 2002, serum samples were sent to Oxford for MuSK antibody testing from 35 centres in 6 continents. MuSK antibodies were identified in 143/465 (30.8%) previously untested SNMG sera. They were not identified in 147 adult acetylcholine receptor antibody positive patients or in 63 adult ocular MG patients. As expected from subsequent reports, the MuSK antibody positive patients differed in gender, clinical severity, bulbar predominance and treatment requirements from the 322/465 (69.2%) MuSK antibody negative SNMG patients, but they were improved following the more aggressive treatments received, although still showing bulbar predominance. Similar features were seen in the 42 childhood cases tested (17/42 (40%) MuSK-Ab positive from 18 centres); although numbers were small there was bulbar predominance that persisted after the treatments that were more extensive than those given to the juvenile SNMG patients. Although found in each continent, MuSK-MG showed an unexpected and surprising distribution. The frequency of MuSK-Abs within individual centres varied in the Northern Hemisphere with a clear north-south gradient from 0% to 47% in Europe and North America. There were fewer cohorts from Asia but data from 11 publications, including five from East and South East Asia, confirmed a latitudinal distribution of MuSK-Ab frequency consistent with a Gaussian curve peaking at 40 degrees North, and trending towards very low frequencies above this latitude in Europe and below this latitude in South East Asia. Thus, MuSK-Abs, that are predominantly IgG4 rather than IgG1 subclass, show a striking and unexpected relationship with latitude in the Northern Hemisphere. The results raise interesting questions regarding the environmental and genetic factors involved, with possible relevance also for the increasing number of IgG4 antibody-mediated neurological disorders, including forms of neuropathy and autoimmune encephalitis.
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| Authors | Angela Vincent, Rehab Badi, Nina Barišić, Sonia Berrih‐Aknin, Domenico Marco Bonifati, Talma Brenner, C H Chalk, Thashi Chang, Hou-Chang Chiu, David Corbin, Elena Cortés-Vicente, Feza Deymeer, Sevim Erdem-Ozdamar, Amelia Evoli, B Eymard, Nils Erik Gilhus, Marc Gotkine, Jeannine M. Heckmann, Zsolt Illes, Leslie Jacobson, Kleopas A. Kleopa, Anna Kostera-Pruszczyk, Satoshi Kuwabara, Robert Lisak, Renato Mantegazza, Arthur Melms, Masakatsu Motomura, Shahriar Nafissi, Michael Nicolle, Joél Oger, Stephen Reddel, Ricardo Roda, R K Rosales, Valeria Salutto, Donald Sanders, Sumit Singh, Marco Spinazzi, Jan J G M Verschuuren, John Vissing, Rawiphan Witoonpanich |
| Journal | Brain research |
| Year | 2026 |
| DOI |
10.1093/brain/awag215
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| URL | |
| Keywords | Keywords not found |
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