Ruggiero, Alessandra 
ORCID: 0000-0001-6436-8814, Pascucci, Giuseppe Rubens, Cotugno, Nicola, Dominguez-Rodriguez, Sara, Rinaldi, Stefano, Tagarro, Alfredo, Rojo, Pablo, Foster, Caroline, Bamford, Alasdair, De Rossi, Anita et al (show 15 more authors)
(2022)
Determinants of B-Cell Compartment Hyperactivation in European Adolescents Living With Perinatally Acquired HIV-1 After Over 10 Years of Suppressive Therapy.
FRONTIERS IN IMMUNOLOGY, 13.
860418-.
|
Text
Determinants of B-Cell Compartment Hyperactivation in European Adolescents Living With Perinatally Acquired HIV-1 After Over.pdf - Open Access published version Download (5MB) | Preview |
Abstract
<h4>Background</h4>Despite a successful antiretroviral therapy (ART), adolescents living with perinatally acquired HIV (PHIV) experience signs of B-cell hyperactivation with expansion of 'namely' atypical B-cell phenotypes, including double negative (CD27-IgD-) and termed age associated (ABCs) B-cells (T-bet+CD11c+), which may result in reduced cell functionality, including loss of vaccine-induced immunological memory and higher risk of developing B-cells associated tumors. In this context, perinatally HIV infected children (PHIV) deserve particular attention, given their life-long exposure to chronic immune activation.<h4>Methods</h4>We studied 40 PHIV who started treatment by the 2<sup>nd</sup> year of life and maintained virological suppression for 13.5 years, with 5/40 patients experiencing transient elevation of the HIV-1 load in the plasma (Spike). We applied a multi-disciplinary approach including immunological B and T cell phenotype, plasma proteomics analysis, and serum level of anti-measles antibodies as functional correlates of vaccine-induced immunity.<h4>Results</h4>Phenotypic signs of B cell hyperactivation were elevated in subjects starting ART later (%DN T-bet+CD11c+ p=0.03; %AM T-bet+CD11c+ p=0.02) and were associated with detectable cell-associated HIV-1 RNA (%AM T-bet+CD11c+ p=0.0003) and transient elevation of the plasma viral load (spike). Furthermore, B-cell hyperactivation appeared to be present in individuals with higher frequency of exhausted T-cells, in particular: %CD4 TIGIT+ were associated with %DN (p=0.008), %DN T-bet+CD11c+ (p=0.0002) and %AM T-bet+CD11c+ (p=0.002) and %CD4 PD-1 were associated with %DN (p=0.048), %DN T-bet+CD11c+ (p=0.039) and %AM T-bet+CD11c+ (p=0.006). The proteomic analysis revealed that subjects with expansion of these atypical B-cells and exhausted T-cells had enrichment of proteins involved in immune inflammation and complement activation pathways. Furthermore, we observed that higher levels of ABCs were associated a reduced capacity to maintain vaccine-induced antibody immunity against measles (%B-cells CD19+CD10- T-bet+, p=0.035).<h4>Conclusion</h4>We identified that the levels of hyperactivated B cell subsets were strongly affected by time of ART start and associated with clinical, viral, cellular and plasma soluble markers. Furthermore, the expansion of ABCs also had a direct impact on the capacity to develop antibodies response following routine vaccination.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | AIDS, B-cell hyperactivation, caHIV-1 RNA, CD11c, exhausted T-cells, late ART, perinatal HIV, proteomic profiling immune activation, T-bet |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 09 Oct 2023 09:56 |
| Last Modified: | 30 Oct 2023 03:06 |
| DOI: | 10.3389/fimmu.2022.860418 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3173524 |
Dimensions
Dimensions
