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Thymoma-associated myasthenia gravis: On the search for a pathogen signature.
- Source :
-
Journal of autoimmunity [J Autoimmun] 2014 Aug; Vol. 52, pp. 29-35. Date of Electronic Publication: 2014 Jan 17. - Publication Year :
- 2014
-
Abstract
- Myasthenia gravis (MG) is an autoimmune disease mainly mediated by anti-acetylcholine receptor (AChR) antibodies. In the late onset, a thymoma, tumor of the thymus, is quite frequent. However, the events leading to thymoma and MG are not understood. As thymoma-associated MG (MG-T) patients also display anti-interferon type I (IFN-I) neutralizing antibodies, we investigated if MG-T could be associated with an anti-viral signature. RT-PCR analyses demonstrated huge increases of IFN-I subtypes, IFN-α2, -α8, -ω and -β, in thymoma-associated MG but not in thymomas without MG or in control thymuses. Next, we investigated if dsRNA signaling pathway involvement could be observed in MG-T, as recently observed in early-onset MG. We observed an abnormal regulation of dsRNA-sensing molecules with an increase of toll-like receptor 3 (TLR3), and a decrease of protein kinase R (PKR) and dsRNA helicases (RIG-I and MDA5) in thymoma from MG patients. We also detected a decreased expression of p53, the tumor suppressor that is known to be down-regulated by dsRNA. Altogether, these results strongly suggest that MG-T could be linked to a viral infection. As p16 (CDKN2A), a marker of HPV infections, was up-regulated in MG-T, we thus screened DNA from thymomas for human papillomavirus (HPV) by real-time PCR using HPV consensus SPF10 primers. RT-PCR results were negative for all samples tested. We confirmed the absence of HPV DNA detection by end point PCR using FAP primers to amplify a larger panel of HPV genotypes. Our data clearly demonstrate INF-I overexpression together with the activation of innate immunity pathways in thymoma-associated MG suggesting that MG might develop after a pathogen infection. We were not able to relate thymoma to HPV infections and the implication of other pathogens is discussed.<br /> (Copyright © 2014 Elsevier Ltd. All rights reserved.)
- Subjects :
- Adult
Aged
Alphapapillomavirus genetics
Antibodies, Viral metabolism
Autoantibodies metabolism
Cells, Cultured
Child, Preschool
Cyclin-Dependent Kinase Inhibitor p16 genetics
DNA, Viral analysis
Female
Gene Expression Regulation
Humans
Immunity, Innate
Infant
Infant, Newborn
Interferon Type I genetics
Interferon Type I immunology
Male
Middle Aged
Myasthenia Gravis etiology
Myasthenia Gravis genetics
Papillomavirus Infections complications
Papillomavirus Infections genetics
Receptors, Cholinergic immunology
Thymoma etiology
Thymoma genetics
Thymus Neoplasms etiology
Thymus Neoplasms genetics
Young Adult
Alphapapillomavirus immunology
Cyclin-Dependent Kinase Inhibitor p16 metabolism
Interferon Type I metabolism
Myasthenia Gravis immunology
Papillomavirus Infections immunology
Thymoma immunology
Thymus Neoplasms immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9157
- Volume :
- 52
- Database :
- MEDLINE
- Journal :
- Journal of autoimmunity
- Publication Type :
- Academic Journal
- Accession number :
- 24440286
- Full Text :
- https://doi.org/10.1016/j.jaut.2013.12.018