AB1062 INTER-LABORATORY COMPARISON OF TYPE I INTERFERON SIGNATURE ANALYSES: PAVING THE WAY TO SHARE RECOMMENDATIONS.
Authors: Alessandra Tesser, Gian Marco Moneta, Antonella Insalaco, Rebecca Nicolai, Claudia Bracaglia, Valentina Moressa, Serena Pastore, Andrea Taddio, Alberto Tommasini, Paola Bocca, Marco Gattorno, Fabrizio De Benedetti, Volpi Stefano
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Interferon (IFN) signature analysis is experimentally used to classify pathological conditions characterized by a type I IFN dysregulation (i.e. monogenic interferonopathies, dermatomyositis, systemic lupus erythematosus), and to formulate targeted therapy approaches.Indeed, IFN signature is used to differentiate patients with IFN-related inflammation from conditions predominantly mediated by other cytokines (e.g. JIA and periodic fevers), through the calculation of an IFN score (IS). However, at the moment, there is not a shared threshold able to discriminate among different inflammatory conditions. <h3>Objectives</h3> To characterize the IS in different inflammatory diseases and evaluate the concordance of IFN signature results among the laboratories of the three Italian Hospitals. <h3>Methods</h3> Assessment of the expression in peripheral blood of six IFN-induced genes (IFI27, IFI44L, IFIT1, ISG15, RSAD2, SIGLEC1) in Real Time PCR, referring to a calibrator sample (healthy controls). Calculation of the "interferon score" (IS) for each patient using the median fold change of the six relative quantifications. 50 patients with different inflammatory disorders considered not related to IFN (e.g. Crohn, JIA, hereditary periodic fevers) were compared with established type I IFN-related diseases (SLE, monogenic interferonopathies, dermatomyositis). We analysed the concordance of the clinical classification of different inflammatory diseases and the IS results.To assess the inter-laboratory variability, twenty patients with different degree of type I IFN inflammation were analysed at three different laboratories. <h3>Results</h3> Despite the IFN signature showed a similar and comparable trend, the IS was not consistent between different laboratories, in particular for samples with higher IS score. Thus, the concordance between clinical classification and IS could be assessed only separately for each laboratory. Although in each series IFN-related disorders showed a IS significantly higher than other kind of inflammatory disorders, preliminary results suggest there is no clear threshold able to differentiate among these groups. <h3>Conclusion</h3> Analysis of type I IFN activation in peripheral blood showed a relevant inter-laboratory variability between our three centers, limiting the possibility of identifying a shared defined threshold to differentiate inflammatory syndromes, and suggesting the need to determine reproducible calibrator samples. Cooperation between different institutes could facilitate the collection of clinical and laboratory data in a common database, to exchange expertise in type I IFN-mediated diseases, and provide practical advices for IFN signature assessment and interpretation in the clinical practice. <h3>Disclosure of Interests</h3> Alessandra Tesser: None declared, Gian Marco Moneta: None declared, Antonella Insalaco: None declared, Rebecca Nicolai: None declared, Claudia Bracaglia: None declared, Valentina Moressa: None declared, Serena Pastore: None declared, Andrea Taddio: None declared, Alberto Tommasini: None declared, Paola Bocca: None declared, Marco Gattorno Grant/research support from: MG has received unrestricted grants from Sobi and Novartis, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Volpi Stefano: None declared