Effect of Antiretroviral Therapy on the Memory and Activation Profiles of B Cells in HIV-Infected African Women

Abstract

HIV infection induces a wide range of effects in B cells, including skewed memory cell differentiation, compromised B cell function and hypergammaglobulinaemia. However, data on the extent to which these B cell abnormalities can be reversed by antiretroviral therapy (ART) are limited. To investigate the effect of ART on B cells, the activation (CD86) and differentiation (IgD, CD27 and CD38) profiles of B cells were measured longitudinally in 19 HIV-infected individuals before (median, 2 months) and after ART initiation (median, 12 months) and compared to 19 age-matched HIV-uninfected individuals, using flow cytometry. Twelve months of ART restored the typical distribution of B cell subsets, increasing the proportion of naive B cells (CD27−IgD+CD38−) and concomitantly decreasing the immature transitional (CD27−IgD+CD38+), unswitched memory (CD27+IgD+CD38−), switched memory (CD27+IgD−CD38− or CD27−IgD−CD38−) and plasmablast (CD27+IgD−CD38high) subsets. However, B cell activation was only partially normalized post-ART, with the frequency of activated B cells (CD86+CD40+) reduced compared to pre-ART levels (p=0.0001), but remaining significantly higher compared to HIV-uninfected individuals (p=0.0001). Interestingly, unlike for T cell activation profiles, the extent of B cell activation prior to ART did not correlate with HIV plasma viral load, but positively associated with plasma sCD14 levels (p=0.01, r=0.58). Overall, ART partially normalizes the skewed B cell profiles induced by HIV, with some activation persisting. Understanding the effect of HIV on B cell dysfunction and restoration following ART may provide important insights into mechanisms of HIV pathogenesis.

Alterations in B Cell Compartment Correlate with Poor Neutralization Response and Disease Progression in HIV-1 Infected Children

“…Restoration of memory B cell responses in progressors post ART in this study is in agreement with previous studies documenting the beneficial effect of early initiation of ART ( 23 , 44 , 56 – 58 ). In 2013, WHO conditionally recommended that all 2- to 5-year-old HIV-1-infected children be placed on HAART, based on studies that demonstrated improvement in clinical and virological parameters post ART ( 52 ).…”

IgG abnormalities in HIV-positive Malawian women initiating antiretroviral therapy during pregnancy persist after 24 months of treatment

“…Again IgG2 levels did not change with ART, remaining at the pre-therapy levels. In agreement with others (Tanko et al, 2017), it was found that the persistence of IgG disorders was not associated with the viral load (undetectable in all women). Indexes of immune activation were not measured in the study women, but it is likely that the persistence of inflammatory cytokines, a hallmark of HIV-induced immune activation status (Brenchley et al, 2006;Mehraj et al, 2019), could have affected IgG isotype switching (Tangye et al, 2002) and subclass synthesis (Kawano et al, 1994).…”

“…It was also found that the high levels of total IgG and IgG1 were not associated with the viral burden, but rather with the CD4+ cell count, suggesting that the T-cell dysfunction could be the primary force leading to the general dysregulation of the immune system (Malaspina et al, 2003). These results are in agreement with those of previous studies that have found IgG abnormalities associated with markers of immunoactivation and to the decline in T-cell functionality (Abudulai et al, 2016D'Orsogna et al, 2007Tanko et al, 2017). The IgG isotype distribution was dominated by IgG1, which represented more than 90% of total IgG, followed by IgG3 (5.3%), while the IgG2 isotype, which accounts for 20-30% of total IgG in the normal population (Vidarsson et al, 2014;Puissant-Lubrano et al, 2015), accounted for only 5.2%.…”

“…infection (Pensieroso et al 2009;Moir et al, 2010). Although the majority of these studies involved patients from developed countries, where better sanitary conditions, a lack of chronic parasite infections, and the wider availability of different therapeutic approaches can have an important impact, analogous effects of ART on the memory B-cells and activation of B-specific markers have been observed in the few studies performed in African cohorts, reporting incomplete recovery of the B-cell anomalies induced by HIV (Longwe et al, 2010;Tanko et al, 2017). This study focused on the IgG profile, since hypergammaglobulinemia in pregnancy has been associated with severe impairment of transplacental passage and can have important consequences for the clinical outcome of the infants (Abu-Raya et al, 2016).…”

Prospects for SARS-CoV-2 diagnostics, therapeutics and vaccines in Africa

“…To date, there are no reports describing immune responses to SARS-CoV-2 in individuals infected with HIV-1. It is possible that individuals with HIV-1 may have incomplete immune reconstitution and impaired immunity that may influence vaccine safety and efficacy, even if they are receiving antiretroviral therapy, owing to persistent immune activation and incomplete recovery of T cell and B cell immunity 123,124 . Suboptimal neutralizing antibody responses have been described following immunization against influenza virus or other pathogens in individuals infected with HIV-1 (ref.…”