Enhanced early IgG-mediated complement deposition in the development of chronic chikungunya virus disease

Abstract

Chikungunya virus (CHIKV) disease typically resolves following acute infection; however, some individuals develop chronic CHIKV disease (CCD) characterized by persistent, debilitating joint pain. Antibodies help clear CHIKV through neutralization and Fc effector functions. Previous studies have associated CCD with a poor neutralizing antibody response; however, the role of Fc effector functions in CCD development remains unclear. Here, purified IgG from post-acute serum of individuals who either resolved CHIKV disease or developed CCD was evaluated for IgG activity and Fc effector functions to identify correlations with disease progression and biomarkers for CCD. Resolution was associated with higher levels of CHIKV-specific IgG and IgG1 and stronger CHIKV neutralization. Regression analysis identified bulk IgG2 as a strong predictor of CHIKV disease progression. Development of CCD was associated with enhanced IgG-mediated complement deposition on infected cells. These findings suggest that localized complement activation at sites of infection may contribute to persistent inflammation underlying CCD.