Autoantibodies neutralizing type I interferons underlie a third of cases of Chikungunya virus encephalitis or myelitis

Chikungunya virus (CHIKV) infection is typically not life-threatening but may, in rare cases, affect the central nervous system (CNS). In three cohorts of confirmed CHIKV cases from Martinique (French overseas territory) and Brazil (patients aged 0–89 years, n = 245), 20 patients had CNS infection (aged 17–87 years). Autoantibodies neutralizing type I interferons (AAN-I-IFN) were found in 35% of patients (4 male and 3 female, aged 17–87 years) with encephalitis (4/15), encephalomyelitis (1/2), or myelitis (2/3), but were absent in 225 patients without CNS infection. They neutralized high concentrations (10–1,000 ng/mL) of IFN-α2, IFN-α8, and IFN-ω, and the antibodies of one patient also neutralized IFN-β. All samples also neutralized the other 10 IFN-α subtypes (at least 100 pg/mL). This combination of blood autoantibodies occurs in ∼0.02% and 0.6% of healthy individuals under and over 70 years of age, respectively. The presence of AAN-I-IFN before CHIKV infection therefore increased the risk of CNS disease ∼850-fold relative to the general population.