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Autoantibody Specificities and Type I Interferon Pathway Activation in Idiopathic Inflammatory Myopathies
L. Ekholm, S. Vosslamber, A. Tjärnlund, TD. de Jong, Z. Betteridge, N. McHugh, L. Plestilova, M. Klein, L. Padyukov, AE. Voskuyl, IE. Bultink, D. Michiel Pegtel, CP. Mavragani, MK. Crow, J. Vencovsky, IE. Lundberg, CL. Verweij,
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu srovnávací studie, časopisecké články
NLK
Free Medical Journals
od 1997 do Před 1 rokem
Medline Complete (EBSCOhost)
od 1972-01-01 do Před 1 rokem
Wiley Free Content
od 1997 do Před 1 rokem
PubMed
27173897
DOI
10.1111/sji.12449
Knihovny.cz E-zdroje
- MeSH
- autoprotilátky imunologie MeSH
- dermatomyozitida imunologie MeSH
- interferon typ I metabolismus MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- myozitida s inkluzními tělísky imunologie MeSH
- prospektivní studie MeSH
- proteiny vázající RNA imunologie MeSH
- senioři MeSH
- signální transdukce MeSH
- specificita protilátek * MeSH
- systémový lupus erythematodes imunologie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Myositis is a heterogeneous group of autoimmune diseases, with different pathogenic mechanisms contributing to the different subsets of disease. The aim of this study was to test whether the autoantibody profile in patients with myositis is associated with a type I interferon (IFN) signature, as in patients with systemic lupus erythematous (SLE). Patients with myositis were prospectively enrolled in the study and compared to healthy controls and to patients with SLE. Autoantibody status was analysed using an immunoassay system and immunoprecipitation. Type I IFN activity in whole blood was determined using direct gene expression analysis. Serum IFN-inducing activity was tested using peripheral blood cells from healthy donors. Blocking experiments were performed by neutralizing anti-IFNAR or anti-IFN-α antibodies. Patients were categorized into IFN high and IFN low based on an IFN score. Patients with autoantibodies against RNA-binding proteins had a higher IFN score compared to patients without these antibodies, and the IFN score was related to autoantibody multispecificity. Patients with dermatomyositis (DM) and inclusion body myositis (IBM) had a higher IFN score compared to the other subgroups. Serum type I IFN bioactivity was blocked by neutralizing anti-IFNAR or anti-IFN-α antibodies. To conclude, a high IFN score was not only associated with DM, as previously reported, and IBM, but also with autoantibody monospecificity against several RNA-binding proteins and with autoantibody multispecificity. These studies identify IFN-α in sera as a trigger for activation of the type I IFN pathway in peripheral blood and support IFN-α as a possible target for therapy in these patients.
Department of Pathology VU University Medical Center Amsterdam the Netherlands
Institute of Rheumatology Prague Czech Republic
Citace poskytuje Crossref.org
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- $a Myositis is a heterogeneous group of autoimmune diseases, with different pathogenic mechanisms contributing to the different subsets of disease. The aim of this study was to test whether the autoantibody profile in patients with myositis is associated with a type I interferon (IFN) signature, as in patients with systemic lupus erythematous (SLE). Patients with myositis were prospectively enrolled in the study and compared to healthy controls and to patients with SLE. Autoantibody status was analysed using an immunoassay system and immunoprecipitation. Type I IFN activity in whole blood was determined using direct gene expression analysis. Serum IFN-inducing activity was tested using peripheral blood cells from healthy donors. Blocking experiments were performed by neutralizing anti-IFNAR or anti-IFN-α antibodies. Patients were categorized into IFN high and IFN low based on an IFN score. Patients with autoantibodies against RNA-binding proteins had a higher IFN score compared to patients without these antibodies, and the IFN score was related to autoantibody multispecificity. Patients with dermatomyositis (DM) and inclusion body myositis (IBM) had a higher IFN score compared to the other subgroups. Serum type I IFN bioactivity was blocked by neutralizing anti-IFNAR or anti-IFN-α antibodies. To conclude, a high IFN score was not only associated with DM, as previously reported, and IBM, but also with autoantibody monospecificity against several RNA-binding proteins and with autoantibody multispecificity. These studies identify IFN-α in sera as a trigger for activation of the type I IFN pathway in peripheral blood and support IFN-α as a possible target for therapy in these patients.
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