OBJECTIVES: To determine whether type 1 interferon (IFN) proteins in blood are associated with downstream type 1 IFN-inducible gene expression in blood from patients with myositis. METHODS: IFNα, IFNβ and IFNω concentrations were measured by ELISA in 129 blood samples (from 93 patients with dermatomyositis (DM), inclusion body myositis, polymyositis and other muscle diseases and from 36 healthy volunteers). Their concentrations were correlated with their ability to stimulate type 1 IFN-inducible gene transcription in a functional assay for 123 of these samples and the type 1 IFN-inducible blood gene expression from 70 of the same samples. RESULTS: Blood IFNβ concentration was uniquely associated with DM (p=0.0004), detectable in 64% of samples from patients with untreated or minimally treated DM and 35% of all DM samples compared with 6% of other inflammatory myopathy and 6% of healthy volunteer samples. Blood IFNβ, but not IFNα or IFNω, correlated with high blood type 1 IFN-inducible gene expression (p=0.01). Healthy volunteer samples with a high ELISA signal for IFNα and IFNω lacked functional bioassay activity and such a signal was confirmed as artefactual. CONCLUSION: Elevated blood IFNβ protein concentration is associated with DM. Systemic and local production of IFNβ might contribute to, but may not fully explain, the marked overproduction of type 1 IFN-inducible transcripts and proteins seen in DM muscle and blood.
OBJECTIVES: To determine whether type 1 interferon (IFN) proteins in blood are associated with downstream type 1 IFN-inducible gene expression in blood from patients with myositis. METHODS:IFNα, IFNβ and IFNω concentrations were measured by ELISA in 129 blood samples (from 93 patients with dermatomyositis (DM), inclusion body myositis, polymyositis and other muscle diseases and from 36 healthy volunteers). Their concentrations were correlated with their ability to stimulate type 1 IFN-inducible gene transcription in a functional assay for 123 of these samples and the type 1 IFN-inducible blood gene expression from 70 of the same samples. RESULTS: Blood IFNβ concentration was uniquely associated with DM (p=0.0004), detectable in 64% of samples from patients with untreated or minimally treated DM and 35% of all DM samples compared with 6% of other inflammatory myopathy and 6% of healthy volunteer samples. Blood IFNβ, but not IFNα or IFNω, correlated with high blood type 1 IFN-inducible gene expression (p=0.01). Healthy volunteer samples with a high ELISA signal for IFNα and IFNω lacked functional bioassay activity and such a signal was confirmed as artefactual. CONCLUSION: Elevated blood IFNβ protein concentration is associated with DM. Systemic and local production of IFNβ might contribute to, but may not fully explain, the marked overproduction of type 1 IFN-inducible transcripts and proteins seen in DM muscle and blood.
Authors: Heiyoung Park; Ariel Bulua Bourla; Daniel L Kastner; Robert A Colbert; Richard M Siegel Journal: Nat Rev Immunol Date: 2012-07-25 Impact factor: 53.106
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