CD4 T cell counts are inversely correlated with anti-gp120 cluster A antibodies in antiretroviral therapy-treated PLWH

作者：Mehdi Benlarbi, Jonathan Richard, Tommaso Clemente, Catherine Bourassa, William D. Tolbert, Suneetha Gottumukkala, Marc Messier-Peet, Halima Medjahed, Marzena Pazgier, Frank Maldarelli, Antonella Castagna, Madéleine Durand, Andrés Finzi · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105856 · 被引用次数：6 · 研究领域：HIV Research and Treatment、Renal Transplantation Outcomes and Treatments、HIV-related health complications and treatments

Background While antiretroviral therapy (ART) efficiently suppresses viral replication, inflammation and immune dysfunction persist in some people living with HIV-1 (PLWH). HIV-1 soluble gp120 (sgp120) has been detected in PLWH plasma and its presence is linked to immune dysfunction. It was reported that sgp120 binding to CD4 on uninfected bystander CD4 + T cells sensitises them to cellular death via antibody-dependent cellular cytotoxicity (ADCC) mediated by non-neutralising anti-cluster A antibodies (Abs) present in PLWH plasma. Methods We included plasma from 520 PLWH on ART from three independent cohorts for measurements of anti-cluster A Abs and anti-CD4 binding site (anti-CD4BS) Abs. Associations between CD4 + T cell counts and anti-cluster A Abs was assessed using generalised least squares linear regression models, adjusting for potential confounders including age, sex, nadir CD4 and duration of ART. The role of anti-CD4BS Abs was evaluated using flow-cytometry based ADCC assays with primary CD4 + T cells. Findings We observed that non-neutralising anti-cluster A Abs are negatively associated with CD4 + T cell counts. Anti-CD4BS antibodies blocked the coating of uninfected bystander cells by sgp120, thereby preventing their elimination by ADCC. Supporting a protective role of anti-CD4BS antibodies, their presence in PLWH plasma abrogated the negative association between CD4 counts and anti-cluster A Abs. Interpretation Our results reveal that anti-cluster A Abs are ass...