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Dysregulation of type I interferon (IFN-I) signalling plays a major role in systemic lupus erythematosus (SLE) pathogenesis.1 Selected IFN-stimulated genes (ISGs) are used to generate scores and were shown to be associated with specific clinical phenotypes, SLE activity, risk of flares and response to treatment targeting IFN-I.2 3 IFN-I gene scores are highly heterogeneous in the number of included ISGs and are not standardised for the use in routine clinical practice. Serum IFN-α levels detected by digital ELISA by single molecule array were shown to be a promising biomarker of SLE activity4 and predictor of flares among patients with SLE in remission.5 IFN-γ may also play a role in SLE pathogenesis and it has been shown that several genes that are upregulated by IFN-α are upregulated also by IFN-γ.6 In the present study, we aimed at assessing whether IFN-I gene score in blood and IFN-α or IFN-γ levels quantified by digital ELISA in serum performed similarly as biomarkers, mirroring the clinical activity of SLE. Moreover, we investigated by correlative evidence the contribution of IFN-α and IFN-γ to the expression levels of different ISGs and of an IFN-I gene score.
Gene expression was assessed by mRNA profiling using the NanoString nCounter gene expression system (NanoString Technologies, Seattle, Washington). Serum IFN-α and IFN-γ levels were quantified by digital ELISA technology (Quanterix Simoa, Lexington, Massachusetts, USA). Detailed methodology is available in online supplemental document S1. The clinical characteristics of the 133 patients with SLE included in the present study …
Footnotes
FC and AM are joint first authors.
Handling editor Josef S Smolen
Twitter @delcourvoisier
FC and AM contributed equally.
Contributors All authors: substantial contributions to the conception or design of the work or the acquisition, analysis or interpretation of data for the work; drafted the work or revised it critically for important intellectual content; final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Funding The work was partially supported by funds provided to CC by an unrestricted research grant by GSK. FC was supported by a research travel grant from the French Society of Dermatology, CEDEF and from Institut Servier, Paris, France. The single molecule array interferon assays were performed with the financial support of the ‘Lupus France’ association. Swiss SLE Cohort Study was supported by the Association of the Swiss SLE Cohort Study.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer reviewed.
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