Type I Interferon Signature: a Quantitative Standardized Method for Clinical Application.

Abstract

Type I Interferon (IFN) induced gene expression analysis ("IFN signature") is employed to categorize pathological conditions that exhibit type I IFN dysregulation and to direct customized therapeutic strategies. For instance, it is used to differentiate patients with IFN-related inflammation from those with conditions primarily mediated by other cytokines, such as juvenile idiopathic arthritis and periodic fevers. Nevertheless, there is currently no standardized method available for clinical practice, and comparing values at different time points or between centers poses a challenge. In this work we described a standardized method based on the development and validation of a synthetic control to solve the problem of test comparison. Inter-assay and inter-laboratory variability were assessed by multiple repeated analyses within the same laboratory, and between two different laboratories involved in the study. The method has been validated by evaluating the IFN signature of 39 patients with inflammatory disorders known to be related or not to type I IFN (i.e. monogenic interferonopathies, SLE, juvenile dermatomyositis, periodic fevers, juvenile idiopathic arthritis). The proposed method proved to be highly reproducible among centers and able to discriminate among IFN-related or non-IFN-related inflammation. The use of a synthetic control minimized the inter-assay and inter-laboratory variability, and thus facilitate data sharing among centers to improve knowledge of IFN-related inflammation and patient's care.