Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling.

The type I interferon system is integral to human antiviral immunity. However, inappropriate stimulation or defective negative regulation of this system can lead to inflammatory disease. We sought to determine the molecular basis of genetically uncharacterized cases of the type I interferonopathy Aicardi-Goutières syndrome, and of other patients with undefined neurological and immunological phenotypes also demonstrating an upregulated type I interferon response. We found that heterozygous mutations in the cytosolic double-stranded RNA receptor gene IFIH1 (MDA5) cause a spectrum of neuro-immunological features consistently associated with an enhanced interferon state. Cellular and biochemica…

Proceedings of the 23rd Paediatric Rheumatology European Society Congress: part one

Etanercept treatment for extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, or psoriatic arthritis : 6-year efficacy and safety data from an open-label trial

Background To describe the 6-year safety and efficacy of etanercept (ETN) in children with extended oligoarticular juvenile idiopathic arthritis (eoJIA), enthesitis-related arthritis (ERA), and psoriatic arthritis (PsA) Methods Patients who completed the 2-year, open-label, phase III CLinical Study In Pediatric Patients of Etanercept for Treatment of ERA, PsA, and Extended Oligoarthritis (CLIPPER) were allowed to enroll in its 8-year long-term extension (CLIPPER2). Children received ETN at a once-weekly dose of 0.8 mg/kg, up to a maximum dose of 50 mg/week. Efficacy assessments included the JIA core set of outcomes, the JIA American College of Rheumatology response criteria (JIA-ACR), and t…

Additional file 1: of Etanercept treatment for extended oligoarticular juvenile idiopathic arthritis, enthesitis-related arthritis, or psoriatic arthritis: 6-year efficacy and safety data from an open-label trial

Table S1. Summary of missing data imputation methods for the responder analysis. Table S2. Disease activity and patient-reported outcomes (observed cases). Table S3. Outcomes specific for enthesitis-related arthritis and psoriatic arthritis (observed cases). Table S4. The most frequent TEAEs, excluding infections and injection site reactions (> 5% in any JIA subtype, by System Organ Class). Figure S1. ACR30–100 and JIA inactive disease response rates (OC vs NRI). Additional Tables (A1 to A4) and Figure A1 related to missing data imputation based on patients’ enrolment status, trial period at cut-off date, and reasons for permanent discontinuation. (DOCX 224 kb)