Journal of Clinical Immunology | 2021
Interferon-β Therapy in a Patient with Incontinentia Pigmenti and Autoantibodies against Type I IFNs Infected with SARS-CoV-2
Abstract
To the Editor, We recently reported the presence of autoantibodies (autoAbs) against at least 14 of the 17 type I interferons (IFNs) underlying life-threatening COVID-19 pneumonia in at least 10% of a large cohort of patients [1]. Patients with inborn errors of the TLR3and IRF7-dependent production and amplification of type I IFNs are also prone to life-threatening COVID-19 pneumonia [2]. These findings suggest that the early administration of IFN-α2 or -β, the two clinically available human type I IFNs, might be beneficial to patients with inborn errors of, or auto-Abs against type I IFN infected with SARS-CoV-2. We recently reported the safety and apparent efficacy of early administration of a single subcutaneous injection of Peg-IFN-α2a in two unrelated patients with autosomal dominant deficiencies of TLR3 and IRF3, whose genetic disorders were diagnosed before SARS-CoV-2 infection [3]. Both patients were treated in the first 7 days of SARS-CoV-2 infection and recovered without developing severe COVID19 pneumonia. The administration of IFN-α2 would probably be ineffective in most patients with auto-Abs against type I IFNs, which typically neutralize high concentrations of IFN-ω and the 13 individual IFN-α, including IFN-α2 in particular, in vitro. Plasmapheresis was recently reported to decrease the titers of blood auto-Abs in hospitalized patients with critical pneumonia [4]. However, this invasive procedure cannot be proposed in the outpatient setting, before the development of severe pneumonia. A more promising option is the early administration of IFN-β, as only 2% of patients with lifethreatening COVID-19 and auto-Abs against type I IFNs have auto-Abs that neutralize IFN-β in the conditions in which other type I IFNs are neutralized. In January 2021, we were contacted by a 24-year-old woman with incontinentia pigmenti (IP), a rare X-linked dominant disorder due to heterozygous loss-of-function variants of IKBKG. We have shown that some of women with IP have auto-Abs against type I IFNs [1], including this patient, who has high titers of neutralizing auto-Abs against IFN-α2 and IFN-ω, but not IFN-β (Fig. 1). The only woman with IP previously reported to have been infected with SARS-CoV2 suffered life-threatening COVID-19 pneumonia and displayed neutralizing auto-Abs against type I IFNs [1]. This led us to screen a cohort of women with IP preemptively for the presence of auto-Abs against type I IFNs, including IFN-β. We informed those with auto-Abs against type IFNs to contact us immediately in case of SARS-CoV-2 infection.