Natural-killer-cell-mediated antibody-dependent cellular cytotoxicity response in acute and recovery phases of chikungunya.

Abstract

Antibody-dependent cellular cytotoxicity (ADCC) mediated by natural killer (NK) cells is well documented in the clearance of various viral infections. Beyond direct virus neutralization, virus-specific antibodies confer protection through effector functions involving ADCC. NK cells have been identified as key contributors in chikungunya pathogenesis. This study evaluates NK cell-mediated ADCC involvement in chikungunya by assessing chikungunya virus (CHIKV)-specific ADCC responses in 56 acute, 56 prolonged, and 44 chronic chikungunya arthritis patients, 23 recovered individuals, and 50 healthy controls. A flow-cytometry-based antibody-dependent heterologous NK cell activation assay was employed, utilizing CD107a and IFN-γ as surrogate markers. Group comparisons were performed using the Mann-Whitney test, binary data were analyzed by Fisher's exact test, and correlations between ADCC response, CHIKV viral loads, total anti-CHIKV IgG, and IgG3 antibody levels were assessed by Spearman rank correlation. P values < 0.05 were considered significant. Persistence of ADCC response was observed in recovered individuals for durations ranging from 3 months to 18 years post-infection, while a progressive decline was noted in patients with chronic chikungunya arthritis. An inverse association between ADCC response and viral load was observed in a subset of acute patients. Recovered individuals demonstrated a positive correlation between ADCC response and plasma anti-CHIKV IgG and IgG3 antibody levels (IgG: r = 0.4503, IgG3: r = 0.4583, p-value < 0.01 for each). Collectively, these findings establish the role of NK cell-mediated ADCC response in chikungunya infection and provide a foundation for future antibody-based therapeutics for chikungunya, particularly utilizing IgG3 antibodies with functional ADCC capacity.