Clinical Management Recommendations for Patients With IFNAR1 Deficiency Syndrome

Introduction IFNAR1 deficiency is a rare condition that can result in severe and life-threatening viral infections caused by natural and live-attenuated viruses. Rate of homozygosity for IFNAR1 p.Glu386*, which results in IFNAR1 deficiency, is approximately 1:6,000 in people of Western Polynesian ancestry [1]. We aim to develop a set of clinical management recommendations based on best-available evidence. Method Review of literature, expert and stakeholder (including Australian Technical Advisory Group on Immunisation [ATAGI], Immunisation Advisory Centre [IMAC] [NZ], Australasian Society of Clinical Immunology and Allergy [ASCIA] Immunodeficiency Committee) consultations, survey of resource availability, and clinical practice. Results Based on currently available evidence from case series, mechanistic studies, and expert opinion confirming an increased susceptibility to viral infections, IFNAR1 deficiency working group recommends the following management strategies: (1) Optimise active immunisation using non-live vaccines, including influenza vaccines and paediatric COVID-19 mRNA vaccines; (2) optimise passive immunisation using antiviral monoclonal antibodies (e.g., palivizumab and nirsevimab) to prevent severe RSV infection and using pooled immunoglobulin (e.g., intravenous immunoglobulin and subcutaneous immunoglobulin) to prevent severe viral infections; (3) prioritised and early access to targeted antiviral medications (e.g., remdesivir and nirmatrelvir/ritonavir for SARS-CoV-2; oseltamivir for influenza 1/2; acyclovir for herpes simplex viruses 1/2); (4) prioritised and early access to post-exposure-prophylaxis (e.g., normal human immunoglobulin for measles and zoster immunoglobulin for varicella); (5) physical isolation measures in the setting of increased viral disease burden in the community (e.g., epidemics) and avoiding travel to virus endemic regions; (6) genetic counselling, family planning, and facilitating access to in vitro fertilization, embryo selection, and post-conception antenatal screening; (7) pre-conception, antenatal, and postnatal optimisation of immunisation status of all household and close contacts (including, e.g., maternal respiratory syncytial virus vaccination); and (8) withhold live viral vaccines (including measles- or yellow fever-containing vaccines). Clinical practice survey results will be presented at 2025 ASCIA Conference. Conclusion Early diagnosis of IFNAR1 deficiency and use of effective interventions are crucial to protect affected individuals from severe and life-threatening viral infections.