Determinants of B-Cell Compartment Hyperactivation in European Adolescents Living With Perinatally Acquired HIV-1 After Over 10 Years of Suppressive Therapy
Copyright © 2022 Ruggiero, Pascucci, Cotugno, Domínguez-Rodríguez, Rinaldi, Tagarro, Rojo, Foster, Bamford, De Rossi, Nastouli, Klein, Morrocchi, Fatou, Smolen, Ozonoff, Di Pastena, Luzuriaga, Steen, Giaquinto, Goulder, Rossi, Levy, Pahwa, Palma and the EPIICAL Consortium..
Background: 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.
Methods: We studied 40 PHIV who started treatment by the 2nd 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.
Results: 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).
Conclusion: 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.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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Enthalten in: |
Frontiers in immunology - 13(2022), Seite 860418 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Ruggiero, Alessandra [VerfasserIn] |
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Links: |
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Themen: |
B-cell hyperactivation |
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Anmerkungen: |
Date Completed 19.04.2022 Date Revised 30.11.2023 published: Electronic-eCollection Citation Status MEDLINE |
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doi: |
10.3389/fimmu.2022.860418 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM339618078 |
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520 | |a Copyright © 2022 Ruggiero, Pascucci, Cotugno, Domínguez-Rodríguez, Rinaldi, Tagarro, Rojo, Foster, Bamford, De Rossi, Nastouli, Klein, Morrocchi, Fatou, Smolen, Ozonoff, Di Pastena, Luzuriaga, Steen, Giaquinto, Goulder, Rossi, Levy, Pahwa, Palma and the EPIICAL Consortium. | ||
520 | |a Background: 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 | ||
520 | |a Methods: We studied 40 PHIV who started treatment by the 2nd 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 | ||
520 | |a Results: 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) | ||
520 | |a Conclusion: 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 | ||
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650 | 4 | |a proteomic profiling immune activation | |
650 | 7 | |a Vaccines |2 NLM | |
700 | 1 | |a Pascucci, Giuseppe Rubens |e verfasserin |4 aut | |
700 | 1 | |a Cotugno, Nicola |e verfasserin |4 aut | |
700 | 1 | |a Domínguez-Rodríguez, Sara |e verfasserin |4 aut | |
700 | 1 | |a Rinaldi, Stefano |e verfasserin |4 aut | |
700 | 1 | |a Tagarro, Alfredo |e verfasserin |4 aut | |
700 | 1 | |a Rojo, Pablo |e verfasserin |4 aut | |
700 | 1 | |a Foster, Caroline |e verfasserin |4 aut | |
700 | 1 | |a Bamford, Alasdair |e verfasserin |4 aut | |
700 | 1 | |a De Rossi, Anita |e verfasserin |4 aut | |
700 | 1 | |a Nastouli, Eleni |e verfasserin |4 aut | |
700 | 1 | |a Klein, Nigel |e verfasserin |4 aut | |
700 | 1 | |a Morrocchi, Elena |e verfasserin |4 aut | |
700 | 1 | |a Fatou, Benoit |e verfasserin |4 aut | |
700 | 1 | |a Smolen, Kinga K |e verfasserin |4 aut | |
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700 | 1 | |a Di Pastena, Michela |e verfasserin |4 aut | |
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700 | 1 | |a Rossi, Paolo |e verfasserin |4 aut | |
700 | 1 | |a Levy, Ofer |e verfasserin |4 aut | |
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700 | 1 | |a Puthanakit, Thanyawee |e investigator |4 oth | |
700 | 1 | |a Kuhn, Louise |e investigator |4 oth | |
700 | 1 | |a Yates, Andrew |e investigator |4 oth | |
700 | 1 | |a Violari, Avy |e investigator |4 oth | |
700 | 1 | |a Otwombe, Kennedy |e investigator |4 oth | |
700 | 1 | |a Vaz, Paula |e investigator |4 oth | |
700 | 1 | |a Lain, Maria Grazia |e investigator |4 oth | |
700 | 1 | |a Nampossa, Tacilta |e investigator |4 oth | |
700 | 1 | |a Naniche, Denise |e investigator |4 oth | |
700 | 1 | |a Fernandez-Luis, Sheila |e investigator |4 oth | |
700 | 1 | |a Lopez, Elisa |e investigator |4 oth | |
700 | 1 | |a Peay, Holly |e investigator |4 oth | |
700 | 1 | |a Spyer, Moira |e investigator |4 oth | |
700 | 1 | |a Calvez, Vincent |e investigator |4 oth | |
700 | 1 | |a Marcelin, Anne-Genevieve |e investigator |4 oth | |
700 | 1 | |a Munoz, Maria Angeles |e investigator |4 oth | |
700 | 1 | |a Dalzini, Annalisa |e investigator |4 oth | |
700 | 1 | |a Petrara, Raffaella |e investigator |4 oth | |
700 | 1 | |a Gartner, Kathleen |e investigator |4 oth | |
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700 | 1 | |a Faggion, Silvia |e investigator |4 oth | |
700 | 1 | |a Pena, Daniel Gomez |e investigator |4 oth | |
700 | 1 | |a Oletto, Andrea |e investigator |4 oth | |
700 | 1 | |a Nardone, Alessandra |e investigator |4 oth | |
700 | 1 | |a Zangari, Paola |e investigator |4 oth | |
700 | 1 | |a Cesare, Silvia Di |e investigator |4 oth | |
700 | 1 | |a Medri, Chiara |e investigator |4 oth | |
700 | 1 | |a Kolesova, Olga |e investigator |4 oth | |
700 | 1 | |a Paganin, Carla |e investigator |4 oth | |
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