Env-Specific IgA from Viremic HIV-Infected Subjects Compromises Antibody-Dependent Cellular Cytotoxicity

Abstract

Elucidating the factors that modulate HIV-specific antibody-dependent cellularcytotoxicity (ADCC) will help to understand its role in HIV immunity. The aim of this study was to determine whether IgA could modify ADCC magnitude in HIV infection, abrogating its protective role. Plasma from 20 HIV+ 36 subjects enrolled during primary HIV infection PHI), 10 chronically infected subjects (Chronics) and 7 Elite Controllers (EC) was used. ADCC was determined using a fluorometric ADCC assay, before and after plasma IgA removal. Data was analyzed using non-parametric statistics. ADCC was documented in 40 80% of PHI enrollment samples and in 100% of PHI 12-month samples, Chronics and ECs; itpeaked after acute infection, reached a plateau in chronic infection and decreased after ART initiation. Significant associations between ADCC and disease progression were only found after IgA plasma removal from 12-month PHI samples: ADCC magnitude not only increased after IgA removal but also correlated with CD4+ T-cell preservation. This work provides evidence that gp120-specific IgA was capable of modifying ADCC responses during natural HIV infection for the first time and adds to similar evidence provided in other settings. Furthermore, it underscores the complexity of ADCC phenomenon and will help to understand its underlying mechanisms.