Autoantibodies neutralizing type I interferons underlie a third of cases of Chikungunya virus encephalitis or myelitis
Tran, V. L.; Gervais, A.; Champeaux, M.-M.; de Souza Sampaio, M. P.; Abel, S. L.; Calmont, I.; do Rosario, M. S.; Schidlowski, L.; Simione, J. D.; Alves, P. A.; Puel, A.; Bastard, P.; Abel, L.; Prando, C.; Franca, R. F. d. O.; de Siqueira, I. C.; Cabie, A.; Cobat, A.; Zhang, S.-Y.; Casanova, J.-L.
Show abstract
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-2, IFN-8, and IFN-{omega}, and the antibodies of one patient also neutralized IFN-{beta}. All samples also neutralized the other 10 IFN- 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.
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