Elevated Complement Activation Fragments and C1q-Binding Circulating Immune Complexes in Varied Phases of Chikungunya Virus Infection.

Abstract

Chikungunya virus (CHIKV) is a causative agent of a disease continuum, ranging from an acute transient chikungunya fever to chronic incapacitating viral arthralgia. The interaction between anti-CHIKV antibodies and the complement system has recently received attention. However, the contribution of complement activation in CHIKV-induced pathologies has not been fully elucidated. The present study was undertaken to delineate the possible contribution of complement activation in CHIKV-induced disease progression. In this study, using plasma specimens of chikungunya patients in the acute, chronic, and recovered phases of infection, we explicated the involvement of complement activation in CHIKV disease progression by ELISAs and Bio-Plex assays. Correlation analysis was carried out to demonstrate interrelation among C1q-binding IgG-containing circulating immune complexes (CIC-C1q), complement activation fragments (C3a, C5a, sC5b-9), and complement-modulated pro-inflammatory cytokines (IL-1β, IL-18,IL-6, andTNF-α). We detected elevated complement activation fragments, CIC-C1q, and complement-modulated cytokines in the varied patient groups compared with the healthy controls, indicating persistent activation of the complement system. Furthermore, we observed statistically significant correlations among CIC-C1q with complement activation fragments and C3a with complement modulatory cytokines IL-1β, IL-6, and IL-18 during the CHIKV disease progression. Taken together, the current data provide insight into the plausible association between CICs, complement activation, subsequent complement modulatory cytokine expression, and CHIKV etiopathology.