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 biochemical assays indicate that these mutations confer a gain-of-function - so that mutant IFIH1 binds RNA more avidly, leading to increased baseline and ligand-induced interferon signaling. Our results demonstrate that aberrant sensing of nucleic acids can cause immune upregulation.

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The provincial prophylactic period aligned with the local fixed-date and prospective methods. However, the adoption of any of the first 2 strategies merits close observation to minimize excess healthcare expenditure. The prospective surveillance of laboratory isolates should be further explored as a preferred option to better define prophylactic periods.

Overall, the risk-scoring tool did not discriminate between low versus moderate- to high-risk RSV-positive term infants who require hospitalization which has cost implications, since universal prophylaxis of this cohort would be financially prohibitive. A larger study is necessary to establish risk factors that more accurately determine RSV hospitalization among term infants.