The Presence of Antibody-Dependent Cell Cytotoxicity–Mediating Antibodies in Kaposi Sarcoma–Associated Herpesvirus–Seropositive Individuals Does Not Correlate with Disease Pathogenesis or Progression

Although the immune response is likely to play a pivotal role in controlling Kaposi sarcoma (KS)-associated herpesvirus (KSHV) and preventing disease development, the exact factors responsible for that control remain ill defined. T cell responses are weak and variable, and neutralizing Abs are more frequently detected in individuals with KS. This suggests a potential role for nonneutralizing Abs, which to date have been largely uninvestigated. Ab-dependent cell cytotoxicity (ADCC) is a common effector function for nonneutralizing Abs and is known to play a protective role in other herpesvirus infections; yet, ADCC has never been investigated in the context of KSHV infection. In this study, we provide, to our knowledge, the first evidence that anti-KSHV Abs are capable of mediating ADCC responses against infected human cells undergoing lytic reactivation. ADCC activity significantly higher than seronegative controls was detected in 24 of 68 KSHV-seropositive individuals tested. However, ADCC responses were not associated with KS development or progression. ADCC activity was also found to be independent of HIV status, sex, age, KSHV Ab titer, and KSHV-neutralizing activity. Nevertheless, additional investigations into effector cell function between KS and asymptomatic individuals are needed to determine whether ADCC has a role in preventing KS.