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

• 成果类型: Article
• 署名作者: Tran, Vu L.; Gervais, Adrian; Champeaux, Marie-Mechtilde; de Souza Sampaio, Maria Paula; Abel, Sylvie; Calmont, Isabelle; do Rosario, Mateus Santana; Schidlowski, Laire; Simione, Jordan D.; Alves, Pedro Augusto; Puel, Anne; Bastard, Paul; Abel, Laurent; Prando, Carolina; Franca, Rafael Freitas de Oliveira; de Siqueira, Isadora Cristina; Cabie, Andre; Cobat, Aurelie; Zhang, Shen-Ying; Casanova, Jean-Laurent
• 署名单位: Rockefeller University; Institut National de la Sante et de la Recherche Medicale (Inserm); Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; Universite Paris Cite; Institut National de la Sante et de la Recherche Medicale (Inserm); CHU Martinique; CHU Martinique; Hospital Pequeno Principe; Hospital Pequeno Principe; Universite Paris Cite; Assistance Publique Hopitaux Paris (APHP); Hopital Universitaire Necker-Enfants Malades - APHP; Hospital Pequeno Principe; Howard Hughes Medical Institute
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2616897123
• 发表日期: 2026-08-25
• 页码: e2616897123
• 关键词: Chikungunya virus; encephalitis; myelitis; type I interferons; autoantibodies; receptor; pathogenesis; cells

摘要

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 to 89 y, n = 245), 20 patients had CNS infection (aged 17 to 87 y). Autoantibodies neutralizing type I interferons (AAN-I-IFN) were found in 35% of patients (4 male and 3 female, aged 17 to 87 y) 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 to 1,000 ng/mL) of IFN-alpha 2, IFN-alpha 8, and IFN-omega, and the antibodies of one patient also neutralized IFN-beta. All samples also neutralized the other 10 IFN-alpha subtypes (at least 100 pg/mL). This combination of blood autoantibodies occurs in similar to 0.02% and 0.6% of healthy individuals under and over 70 y of age, respectively. The presence of AAN-I-IFN before CHIKV infection therefore increased the risk of CNS disease similar to 850-fold relative to the general population.