TYPE I INTERFERON ACTIVATION IN A COHORT OF PATIENTS FROM THE EUROFEVER REGISTRY: CLINICAL AND MOLECULAR ANALYSIS

The role of type I interferon (IFN-I) in autoimmune and autoinflammatory diseases has been widely demonstrated, but its diagnostic role in clinical practice remains a controversial topic. We evaluated 214 consecutive patients, enrolled in the Eurofever Registry with defined or undefined pediatric conditions, for IFN-I activation using real-time quantitative PCR. IFN-I signature was calculated as the median of the relative quantification of six IFN-I -inducible genes compared to healthy controls. Lymphoid involvement was more frequent among patients with activation of the IFN-I pathway (34.5% vs. 20%; p<0.02) compared to IFN-I negative patients. All patients presenting with erythema nodosum had a positive IFN-I score. A significant percentage of patients with activation of the IFN-I pathway had autoantibodies, confirming the strong link between autoimmunity and innate immune activation. We identified 14 patients with genetically determined interferonopathy, 18 with autoinflammatory diseases, 69 with autoimmune disorders, 5 with immunodeficiency and 108 patients presenting with other conditions, including undifferentiated systemic autoinflammatory diseases (USAID) (69/198) and undifferentiated recurrent fever syndrome (SURF) (7/108). Most of the patients affected by systemic erythematosus lupus (SLE) revealed a positive IFN-I signature and six patients with interferonopathies showed a phenotype similar to SLE. The latter had a significantly lower median age at onset and high median values of the interferon signature. These findings could be indicators of the presence of a monogenic disease in patients with atypical SLE. Six patients in this cohort received JAK inhibitors, with a good response in the absence of adverse effects. The possibility of targeted treatment by JAK kinase inhibitors is the real advantage of early genetic diagnosis with the aim of preventing organ damage and reducing the use of steroid therapy or other immunosuppressants.