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Genetic control of autoantibody expression in autoimmune myasthenia gravis: role of the self-antigen and of HLA-linked loci

Genes & Immunity volume 5, pages 398–404 (2004)Cite this article

Abstract

Autoantibodies against the muscle acetylcholine receptor (AChR) play an essential role in the pathophysiology of autoimmune myasthenia gravis (MG). Their serum titers, however, vary considerably among patients. Our aim was to investigate whether their variation might be explained by genetic factors. Using different methods, we have obtained strong evidence for a three-locus association influencing autoantibody titers in MG patients with thymus hyperplasia or with a normal thymus. Two of the loci, one encoding the AChR α-subunit, the other encoding the α-chain of the class II antigen-presentation molecule, HLA-DQ, demonstrated interaction to determine high autoantibody titers. The third locus was associated with the 8.1 ancestral HLA haplotype. It exerted an additive effect and it is posutlated to have a nonantigen specific immunoregulatory function. Our study demonstrates for the first time that polymorphism of an autoantigen gene may quantitatively modify the immune response against it. Altogether, the data lend support to a three-gene model to explain autoantibody expression in a subset of MG patients.

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Acknowledgements

This work was funded by INSERM, the Association Française contre les Myopathies and the Fondation pour la Recherche Médicale. We are most grateful to the participating patients and their families. We thank Dr Charles Bourquin for decisive help with patients recruitment, Ms Catherine Beauvais-Hue for skillful technical assistance, Ms Claire Vandiedonck for critical reading of the manuscript.

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Authors and Affiliations

  1. INSERM U580, Hôpital Necker, Paris, France

    M Giraud, G Beaurain & H-J Garchon

  2. Association Claude Bernard, Paris, France

    G Beaurain

  3. Service de Neurologie, Institut de Myologie, Hôpital de la Salpêtrière, Paris, France

    B Eymard

  4. Service de Neurologie, Hôpital Civil, CHRU, Strasbourg, France

    C Tranchant

  5. Service de Réanimation, Hôpital Raymond Poincaré, Garches, France

    P Gajdos

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  1. M Giraud
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Correspondence to H-J Garchon.

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Giraud, M., Beaurain, G., Eymard, B. et al. Genetic control of autoantibody expression in autoimmune myasthenia gravis: role of the self-antigen and of HLA-linked loci. Genes Immun 5, 398–404 (2004). https://doi.org/10.1038/sj.gene.6364110

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