Cargando…
Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept
Emerging data suggest that costimulation blockade with belatacept effectively controls humoral alloimmune responses. However, whether this effect may be deleterious for protective anti-infectious immunity remains poorly understood. We performed a mechanistic exploratory study in 23 kidney transplant...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374104/ https://www.ncbi.nlm.nih.gov/pubmed/35967428 http://dx.doi.org/10.3389/fimmu.2022.918887 |
_version_ | 1784767719624671232 |
---|---|
author | Pernin, Vincent Meneghini, Maria Torija, Alba Jouve, Thomas Del Bello, Arnaud Sanz-Muñoz, Iván Eiros, Jose Maria Donadeu, Laura Polo, Carol Morandeira, Francisco Navarro, Sergio Masuet, Cristina Favà, Alexandre LeQuintrec, Moglie Kamar, Nassim Crespo, Elena Bestard, Oriol |
author_facet | Pernin, Vincent Meneghini, Maria Torija, Alba Jouve, Thomas Del Bello, Arnaud Sanz-Muñoz, Iván Eiros, Jose Maria Donadeu, Laura Polo, Carol Morandeira, Francisco Navarro, Sergio Masuet, Cristina Favà, Alexandre LeQuintrec, Moglie Kamar, Nassim Crespo, Elena Bestard, Oriol |
author_sort | Pernin, Vincent |
collection | PubMed |
description | Emerging data suggest that costimulation blockade with belatacept effectively controls humoral alloimmune responses. However, whether this effect may be deleterious for protective anti-infectious immunity remains poorly understood. We performed a mechanistic exploratory study in 23 kidney transplant recipients receiving either the calcineurin-inhibitor tacrolimus (Tac, n=14) or belatacept (n=9) evaluating different cellular immune responses after influenza vaccination such as activated T follicular Helper (Tfh), plasmablasts and H1N1 hemagglutinin (HA)-specific memory B cells (HA(+)mBC) by flow-cytometry, and anti-influenza antibodies by hemagglutination inhibition test (HI), at baseline and days 10, 30 and 90 post-vaccination. The proportion of CD4+CD54RA-CXCR5+ Tfh was lower in belatacept than Tac patients at baseline (1.86%[1.25-3.03] vs 4.88%[2.40-8.27], p=0.01) and remained stable post-vaccination. At M3, HA(+)mBc were significantly higher in Tac-treated patients (0.56%[0.32-1.49] vs 0.27%[0.13-0.44], p=0.04) and correlated with activated Tfh numbers. When stratifying patients according to baseline HA(+)mBc frequencies, belatacept patients with low HA(+)mBC displayed significantly lower HA(+)mBc increases after vaccination than Tac patients (1.28[0.94-2.4] vs 2.54[1.73-5.70], p=0.04). Also, belatacept patients displayed significantly lower seroprotection rates against H1N1 at baseline than Tac-treated patients (44.4% vs 84.6%) as well as lower seroconversion rates at days 10, 30 and 90 after vaccination (50% vs 0%, 63.6% vs 0%, and 63.6% vs 0%, respectively). We show the efficacy of belatacept inhibiting T-dependent antigen-specific humoral immune responses, active immunization should be highly encouraged before starting belatacept therapy. |
format | Online Article Text |
id | pubmed-9374104 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93741042022-08-13 Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept Pernin, Vincent Meneghini, Maria Torija, Alba Jouve, Thomas Del Bello, Arnaud Sanz-Muñoz, Iván Eiros, Jose Maria Donadeu, Laura Polo, Carol Morandeira, Francisco Navarro, Sergio Masuet, Cristina Favà, Alexandre LeQuintrec, Moglie Kamar, Nassim Crespo, Elena Bestard, Oriol Front Immunol Immunology Emerging data suggest that costimulation blockade with belatacept effectively controls humoral alloimmune responses. However, whether this effect may be deleterious for protective anti-infectious immunity remains poorly understood. We performed a mechanistic exploratory study in 23 kidney transplant recipients receiving either the calcineurin-inhibitor tacrolimus (Tac, n=14) or belatacept (n=9) evaluating different cellular immune responses after influenza vaccination such as activated T follicular Helper (Tfh), plasmablasts and H1N1 hemagglutinin (HA)-specific memory B cells (HA(+)mBC) by flow-cytometry, and anti-influenza antibodies by hemagglutination inhibition test (HI), at baseline and days 10, 30 and 90 post-vaccination. The proportion of CD4+CD54RA-CXCR5+ Tfh was lower in belatacept than Tac patients at baseline (1.86%[1.25-3.03] vs 4.88%[2.40-8.27], p=0.01) and remained stable post-vaccination. At M3, HA(+)mBc were significantly higher in Tac-treated patients (0.56%[0.32-1.49] vs 0.27%[0.13-0.44], p=0.04) and correlated with activated Tfh numbers. When stratifying patients according to baseline HA(+)mBc frequencies, belatacept patients with low HA(+)mBC displayed significantly lower HA(+)mBc increases after vaccination than Tac patients (1.28[0.94-2.4] vs 2.54[1.73-5.70], p=0.04). Also, belatacept patients displayed significantly lower seroprotection rates against H1N1 at baseline than Tac-treated patients (44.4% vs 84.6%) as well as lower seroconversion rates at days 10, 30 and 90 after vaccination (50% vs 0%, 63.6% vs 0%, and 63.6% vs 0%, respectively). We show the efficacy of belatacept inhibiting T-dependent antigen-specific humoral immune responses, active immunization should be highly encouraged before starting belatacept therapy. Frontiers Media S.A. 2022-07-29 /pmc/articles/PMC9374104/ /pubmed/35967428 http://dx.doi.org/10.3389/fimmu.2022.918887 Text en Copyright © 2022 Pernin, Meneghini, Torija, Jouve, Del Bello, Sanz-Muñoz, Eiros, Donadeu, Polo, Morandeira, Navarro, Masuet, Favà, LeQuintrec, Kamar, Crespo and Bestard https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Pernin, Vincent Meneghini, Maria Torija, Alba Jouve, Thomas Del Bello, Arnaud Sanz-Muñoz, Iván Eiros, Jose Maria Donadeu, Laura Polo, Carol Morandeira, Francisco Navarro, Sergio Masuet, Cristina Favà, Alexandre LeQuintrec, Moglie Kamar, Nassim Crespo, Elena Bestard, Oriol Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept |
title | Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept |
title_full | Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept |
title_fullStr | Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept |
title_full_unstemmed | Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept |
title_short | Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept |
title_sort | impaired antigen-specific b-cell responses after influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with belatacept |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9374104/ https://www.ncbi.nlm.nih.gov/pubmed/35967428 http://dx.doi.org/10.3389/fimmu.2022.918887 |
work_keys_str_mv | AT perninvincent impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT meneghinimaria impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT torijaalba impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT jouvethomas impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT delbelloarnaud impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT sanzmunozivan impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT eirosjosemaria impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT donadeulaura impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT polocarol impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT morandeirafrancisco impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT navarrosergio impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT masuetcristina impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT favaalexandre impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT lequintrecmoglie impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT kamarnassim impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT crespoelena impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept AT bestardoriol impairedantigenspecificbcellresponsesafterinfluenzavaccinationinkidneytransplantrecipientsreceivingcostimulationblockadewithbelatacept |