Env-specific IgA from Viremic HIV-infected Subjects Compromises Antibody-Dependent Cellular Cytotoxicity

MARÍA RUIZ.; YANINA GHIGLIONE; JULIANA FALIVENE; NATALIA LAUFER; MARÍA HOLGADO; MARÍA SOCÍAS; PEDRO CAHN; OMAR SUED; LUIS GIAVEDONI; HORACIO SALOMÓN; M.MAGDALENA GHERARDI; ANA M. RODRÍGUEZ; GABRIELA TURK

JOURNAL OF VIROLOGY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2016

0022-538X

Elucidating the factors that modulate HIV-specific antibody-dependent cellular cytotoxicity (ADCC) will help in understandingits role in HIV immunity. The aim of this study was to determine whether IgA could modify the magnitude of ADCC in HIV infection,abrogating its protective role. Plasma samples from 20 HIV-positive (HIV) subjects enrolled during primary HIV infection(PHI), 10 chronically infected subjects (chronic), and 7 elite controllers (EC) were used. ADCC was determined by using afluorometric ADCC assay, before and after removal of plasma IgA. Data were analyzed by using nonparametric statistics. ADCCwas documented in 80% of PHI enrollment samples and in 100% of PHI 12-month, chronic, and EC samples; it peaked afteracute infection, reached a plateau in chronic infection, and decreased after initiation of antiretroviral treatment (ART). Significantassociations between ADCC and disease progression were found only after removal of plasma IgA from 12-month PHI samples:the magnitude of ADCC not only increased after IgA removal but also correlated with CD4 T-cell preservation. This workprovides evidence that gp120-specific IgA was capable of modifying ADCC responses during natural HIV infection for the firsttime and adds to similar evidence provided in other settings. Furthermore, it underscores the complexity of the ADCC phenomenonand will help in an understanding of its underlying mechanisms.