FRI0542 CLINICAL PRESENTATION, GENETIC ANALYSIS AND IFN-SCORE IN PATIENTS WITH UNDEFINED INTERFERONOPATHIES
Authors: Silvia Federici, Gian Marco Moneta, Chiara Passarelli, Claudia Bracaglia, Gerarda Luana Raffaele, Fabrizio De Benedetti, Antonella Insalaco
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In the last years, an expanding group of complex genetic disorders characterized by disturbance of the homeostatic control of IFN-mediated immune responses, have been identified, so called type I interferonopathies. An increased expression of type I IFN regulated genes, IFN signature (IS), is described in these conditions. IS represent a useful tool in clinical practice to classify patients with suspected interferonopathies. <h3>Objectives</h3> To evaluate the correlation between clinical presentation, genetic analysis and IFN-score in 10 patients with undefined interpheronopathies <h3>Methods</h3> Patients with suspected interferonopathy based on the presence of typical clinical manifestations (neurological, muco-cutaneous symptoms), laboratory parameters (complement deficiency, low platelet count, presence of autoimmunity), instrumental abnormalities (cerebral calcification), were screened for the IFN-score. Defined IFN-mediated diseases were excluded. Patients presenting with a high IFN-score value (above a fixed cut-off of 10) underwent genetic screening by running a panel of 24 genes known to be involved in interferonopathies <h3>Results</h3> 10 patients with suspected interferonopathy followed in a single pediatric rheumatology center were included. 7/10 presented with recurrent episodes of fever (table). Patient 2, 3 and 7 displayed neurological manifestation, respectively epilepsy, epilepsy and mental retardation and progressive hemiplegia. To note epilepsy in patient 2 might be correlated to a bilateral intraventricular hemorrhage presented at birth. In two patients (1,4) gastrointestinal manifestation resembling inflammatory bowel diseases were described while patients 5,7 and 10 suffered from recurrent abdominal pain, diarrhea and patient 10 from hypertransaminasemia. Half of the patients complained arthromyalgia; arthritis developed in patient 2. Cutaneous involvement presented in 3 patients (1,3,6) respectively with a widespread panniculitis of trunk and limbs, aspecific vasculitis and Schonlein Henoch purpura. Other cutaneous manifestation were urticarial rash (pt 2) and an erythematous, desquamative confluent eczema (pt 4). Autoimmunity was confirmed in 2/10 patients. Two patients (4, 8) had an immunological defect with recurrent infections. The genetic analysis resulted negative in patients 1 and 7 and is still ongoing in patients 5, 6 and 8. Patients 2,3,4,9 and 10 carried one mutation in at least one IFN correlated gene not confirming the diagnosis. All patients presented an increased IS ranging from 14,2 to 172,5 <h3>Conclusion</h3> An elevated IFN-score represent a useful instrument in the clinical practice to classify patients with suspected interferonopathy. It may represent an important tool to select those patients to be genetically screened with a defined panel of interferonopathies correlated genes. In those patients in which the genetic analysis result negative, the presence of a positive IFN-score, confirming an activation of this inflammatory pathway, may guide the clinicians in the management of these patients and may support therapeutic decisions <h3> Disclosure of Interests</h3> Silvia Federici: None declared, Gian Marco Moneta: None declared, Chiara Passarelli: None declared, Claudia Bracaglia: None declared, Carmela Gerarda Luana Raffaele: None declared, Fabrizio De Benedetti Grant/research support from: Abbvie, SOBI, Novimmune, Roche, Novartis, Sanofi, Pfizer, Antonella Insalaco: None declared