Background: Type I interferons (IFNs) are involved in the antiviral response and in the pathophysiology of some autoimmune diseases such as type I interferonopathies. Secreted at femtomolar concentrations during the disease course, detection of type I IFN in these patients remains challenging. This issue has led several groups to develop an alternative strategy for the detection of this group of cytokines. Based on quantification of expression of IFN-stimulated genes, blood transcriptional IFN signatures have been developed and are currently used for the screening of patients with interferonopathies.
Distinguishing between bacterial and viral infectious etiologies in febrile patients remains challenging, especially in children. Misdiagnosis of disease etiology is responsible for inappropriate antibiotic prescriptions. We hypothesized that specific host biomarkers for viral infections, like type I-IFN, could help clinician decisions and limit antibiotic overuse.
Materials/methods: This is an ancillary study of the prospective multicentric protocol ANTOINE (NCT03163628). Paxgene® tubes and serum were collected from febrile children aged from 7 days to 36 months with proven viral (n=17) or bacterial (n=33) infection admitted in pediatric emergency departments in France. We have assessed the performance of IFN signature calculated using Nanostring® technology and plasma IFNα quantified by digital ELISA technology (Quanterix®).
Results: Serum level of IFN-α were below the quantification threshold (30fg/mL) for 6% (1/17) and 67% (22/33) of children with proven viral and bacterial infection respectively. IFN-α levels were significantly higher in viral compared to bacterial infection (median [IQR] 5112 [559; 10141] and 132 [37; 3708] fg/mL respectively, p<0.001). We noticed a strong correlation between serum IFN-α concentrations and IFN score (p-pearson=0.83 [CI 95% 0.75, 0.89]). Both serum level IFN-α and IFN score robustly discriminated (AUC 0.88 [CI 95%-0.78, 0.99] and 0.85 [0.72, 0.97] respectively) between viral and bacterial infection in febrile children.
Conclusions: Our study suggests that measurement of IFN-α femtomolar concentrations as well as IFN signature could offer new perspectives for improving diagnosis and limiting antibiotic overuse in febrile children. Our patient recruitment and investigations are still ongoing to ultimately confirm if these markers could become key biomarkers in the decision-making process of clinicians dealing with febrile children.