Type I interferons and their autoantibodies in the context of systemic lupus erythematosus

PurposeType I IFNs and their autoantibodies are implicated in the pathogenesis of Systemic lupus erythematosus (SLE), but their incidence and importance is still unclear. Neutralizing autoantibodies against IFNα have been previously reported in patients with autoimmune polyendocrinopathy syndrome type I (APS-1), rheumatoid arthritis, thymoma and more recently life-threatening COVID-19 patients. We hypothesized that autoantibodies towards type I IFNs, that develop in some patients with SLE, are neutralizing and may interfere with the course of the disease.MethodsLuciferase immunoprecipitation (LIPS) analysis was used to screen 474 SLE patient and 312 control serum samples for the presence of IFNα binding autoantibodies and determine their subclasses. Type I IFN neutralizing capacity was tested using a reporter cell line. Circulating levels of IFNα were measured with Single Molecule Array (Simoa).Results14% of SLE patients were positive for anti-IFNα and 13% were positive for anti-IFNω. The autoantibodies against IFNα were predominantly of IgG1 subclass and neutralized IFNα bioactivity in approximately one half of the positive cases. Once developed, anti-IFNα autoantibodies were present throughout the disease course. IFNα2 and -α8 were targeted first in two informative follow-up cases. The reactivity broadened to other IFNα subtypes and IFNω within several months. Serum levels of IFNα correlated negatively with anti-IFNα neutralizing titers. Patients with high levels of autoantibodies against IFNα had significantly lower levels of circulating IFNα compared to anti-IFNα negative patients. Interestingly, patients with high IFNα neutralizing capacity displayed significantly lower disease activity than patients without these autoantibodies.ConclusionsBased on our results we suggest that autoantibodies that are able to neutralize the circulating levels of all IFNα subtypes may have a beneficial effect to SLE disease course.

Use of Virtual Reality for Pediatric Cardiac Critical Care Simulation.

Simulation is a key component of training in the pediatric cardiac intensive care unit (CICU), a complex environment that lends itself to virtual reality (VR)-based simulations. However, VR has not been previously described for this purpose. Two simulations were developed to test the use of VR in simulating pediatric CICU clinical scenarios, one simulating junctional ectopic tachycardia and low cardiac output syndrome, and the other simulating acute respiratory failure in a patient with suspected coronavirus disease 2019. Six attending pediatric cardiac critical care physicians were recruited to participate in the simulations as a pilot test of VR's feasibility for educational and practice improvement efforts in this highly specialized clinical environment. All participants successfully navigated the VR environment and met the critical endpoints of the two clinical scenarios. Qualitative feedback was overall positive with some specific critiques regarding limited realism in some mechanical aspects of the simulation. This is the first described use of VR in pediatric cardiac critical care simulation.