Determinants of B-Cell Compartment Hyperactivation in European Adolescents Living With Perinatally Acquired HIV-1 After Over 10 Years of Suppressive Therapy.
B-cell hyperactivation
CD11c
T-bet
caHIV-1 RNA
exhausted T-cells
late ART
perinatal HIV/AIDS
proteomic profiling immune activation
Journal
Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960
Informations de publication
Date de publication:
2022
2022
Historique:
received:
22
01
2022
accepted:
03
03
2022
entrez:
18
4
2022
pubmed:
19
4
2022
medline:
20
4
2022
Statut:
epublish
Résumé
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. We studied 40 PHIV who started treatment by the 2 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). 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.
Sections du résumé
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 2
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.
Identifiants
pubmed: 35432380
doi: 10.3389/fimmu.2022.860418
pmc: PMC9009387
doi:
Substances chimiques
Vaccines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
860418Subventions
Organisme : NIAID NIH HHS
ID : P30 AI073961
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127347
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI133673
Pays : United States
Organisme : NIAID NIH HHS
ID : U01 AI135941
Pays : United States
Investigateurs
Mark Cotton
(M)
Shaun Barnabas
(S)
Thanyawee Puthanakit
(T)
Louise Kuhn
(L)
Andrew Yates
(A)
Avy Violari
(A)
Kennedy Otwombe
(K)
Paula Vaz
(P)
Maria Grazia Lain
(MG)
Tacilta Nampossa
(T)
Denise Naniche
(D)
Sheila Fernandez-Luis
(S)
Elisa Lopez
(E)
Holly Peay
(H)
Moira Spyer
(M)
Vincent Calvez
(V)
Anne-Genevieve Marcelin
(AG)
Maria Angeles Munoz
(MA)
Annalisa Dalzini
(A)
Raffaella Petrara
(R)
Kathleen Gartner
(K)
Lesley De Armas
(L)
Pahwa Rajendra
(P)
Suresh Pallikkuth
(S)
Deborah Persaud
(D)
Nicolas Chomont
(N)
Mathias Lichterfeld
(M)
Silvia Faggion
(S)
Daniel Gomez Pena
(DG)
Andrea Oletto
(A)
Alessandra Nardone
(A)
Paola Zangari
(P)
Silvia Di Cesare
(SD)
Chiara Medri
(C)
Olga Kolesova
(O)
Carla Paganin
(C)
William James
(W)
Inger Lindfors-Rossi
(I)
Shrabon Samiur Hassan
(SS)
Francesca Mazzetto
(F)
Hellen Akisinku
(H)
Musakanya Chingandu
(M)
Francesca Rocchi
(F)
Ilaria Pepponi
(I)
Rob J De Boer
(RJ)
Juliane Schroter
(J)
Viviana Giannuzzi
(V)
Andrew Yates
(A)
Sinead Morris
(S)
Informations de copyright
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.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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