An Easy and Reliable Strategy for Making Type I Interferon Signature Analysis Comparable among Research Centers.

Alberto Tommasini,Andrea Taddio,Alessia Pin,Alessandra Tesser,Lorenzo Monasta,Elisa Piscianz

doi:10.3390/diagnostics9030113

Alberto Tommasini, Andrea Taddio + Show 4 more

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https://doi.org/10.3390/diagnostics9030113

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Abstract

Interferon-stimulated genes (ISGs) are a set of genes whose transcription is induced by interferon (IFN). The measure of the expression of ISGs enables calculating an IFN score, which gives an indirect estimate of the exposition of cells to IFN-mediated inflammation. The measure of the IFN score is proposed for the screening of monogenic interferonopathies, like the Aicardi-Goutières syndrome, or to stratify subjects with systemic lupus erythematosus to receive IFN-targeted treatments. Apart from these scenarios, there is no agreement on the diagnostic value of the score in distinguishing IFN-related disorders from diseases dominated by other types of cytokines. Since the IFN score is currently measured in several research hospitals, merging experiences could help define the potential of scoring IFN inflammation in clinical practice. However, the IFN score calculated at different laboratories may be hardly comparable due to the distinct sets of IFN-stimulated genes assessed and to different controls used for data normalization. We developed a reliable approach to minimize the inter-laboratory variability, thereby providing shared strategies for the IFN signature analysis and allowing different centers to compare data and merge their experiences.

Highlights

Type I interferon (IFN) production is part of the innate immune response to viruses or intracellular bacteria, which is triggered by the sensing of pathogen-associated nucleic acids [1]
The measure of expression of the Interferon-stimulated genes (ISGs) (IFN signature analysis) is increasingly used in biomedical research centers, as well as for the functional classification of other conditions characterized by a type I IFN dysregulation [10], to distinguish such conditions from classical inflammatory disorders predominantly mediated by other cytokines, like Tumor Necrosis Factor α and Interleukin 1 [11]
To establish whether data from quantitative PCR (qPCR) and RNAseq analysis were comparable, IFN signature on wet and in silico analysis was performed in twenty subjects with inflammatory diseases, such as systemic lupus erythematosus (SLE), interferonopathies or inflammatory bowel diseases (IBD), and patients’ relatives, recruited at our center (Dataset E)

Summary

Introduction

Type I interferon (IFN) production is part of the innate immune response to viruses or intracellular bacteria, which is triggered by the sensing of pathogen-associated nucleic acids [1]. Even though the identification of IFNs dates back to the 50s–60s [2], the description of a group of mendelian disorders with dysregulated IFN-mediated inflammation has only recently shed light on the fine regulation of the production and action of these cytokines [3]. Of note, this new group of disorders, known as type I interferonopathies, displays significant phenotypic overlaps with both systemic lupus erythematosus (SLE) and congenital viral infections of the TORCH (Toxoplasmosis, Rubella, Cytomegalovirus, Herpes simplex) and HIV (human immunodeficiency virus) groups [3,4]. The measure of expression of the ISGs (IFN signature analysis) is increasingly used in biomedical research centers, as well as for the functional classification of other conditions characterized by a type I IFN dysregulation [10], to distinguish such conditions from classical inflammatory disorders predominantly mediated by other cytokines, like Tumor Necrosis Factor α and Interleukin 1

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