A susceptibility region for myasthenia gravis extending into the HLA-class I sector telomeric to HLA-C

M. Janer; A. Cowland; J. Picard; D. Campbell; P. Pontarotti; J. Newsom-Davis; M. Bunce; K. Welsh; A. Demaine; A.G. Wilson; N. Willcox

doi:10.1016/S0198-8859(99)00062-2

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A susceptibility region for myasthenia gravis extending into the HLA-class I sector telomeric to HLA-C

Journal article

Peer reviewed

A susceptibility region for myasthenia gravis extending into the HLA-class I sector telomeric to HLA-C

M. Janer, A. Cowland, J. Picard, D. Campbell, P. Pontarotti, J. Newsom-Davis, M. Bunce, K. Welsh, A. Demaine, A.G. Wilson, …

Human Immunology, Vol.60(9), pp.909-917

1999

DOI: https://doi.org/10.1016/S0198-8859(99)00062-2

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Abstract

We have analyzed a series of HLA region markers in 207 UK Caucasoids with early-onset myasthenia gravis (EOMG, onset before age 40), where there is a strong female bias. The well known associations with HLA-DR3 and -B8 have now proved to be significantly stronger in the 165 females than in the 42 males. In patients (of either sex) lacking -DR3, there was also a significant increase in HLA-DR2. Although the muscle weakness in EOMG is clearly mediated by autoantibodies, the associations are consistently stronger with HLA-B8 (in class I) than with HLA-DR3 (in class II), as confirmed here. We therefore typed 87–137 cases for polymorphisms at four loci in the intervening class III region, and also at three in the adjacent stretch of class I. At each locus, one allele tended to co-occur with HLA-B8 and showed strong and highly significant associations in the patients. There appeared to be a region of maximal susceptibility extending from HSP70 (in class III) past HLA-B and HLA-C at least 600kb telomerically into the class I region, which is now being mapped in detail. Any candidate genes here that act shortly after puberty may allow more precise localization of susceptibility.

Details

Title: A susceptibility region for myasthenia gravis extending into the HLA-class I sector telomeric to HLA-C
Authors/Creators: M. Janer (Author/Creator) - John Radcliffe Hospital
A. Cowland (Author/Creator) - John Radcliffe Hospital
J. Picard (Author/Creator) - Hammersmith Hospital
D. Campbell (Author/Creator) - The UK HGMP Resource Centre, Hinxton, Cambridge, UK (D.C.)
P. Pontarotti (Author/Creator) - Fondation Jean Dausset-CEPH
J. Newsom-Davis (Author/Creator) - John Radcliffe Hospital
M. Bunce (Author/Creator) - Churchill Hospital
K. Welsh (Author/Creator) - Churchill Hospital
A. Demaine (Author/Creator) - Plymouth Hospital
A.G. Wilson (Author/Creator) - Royal Hallamshire Hospital
N. Willcox (Author/Creator) - John Radcliffe Hospital
Publication Details: Human Immunology, Vol.60(9), pp.909-917
Publisher: Elsevier BV
Identifiers: 991005542082207891
Copyright: 1999 American Society for Histocompatibility and Immunogenetics
Murdoch Affiliation: Murdoch University
Language: English
Resource Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.203 Neuromuscular Disorders; 1.203.1325 Thymectomy in Myasthenia
Web Of Science research areas: Immunology
ESI research areas: Immunology