Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept
Pernin, Vincent (University Hospital of Montpellier (França))
Meneghini, Maria (Hospital Universitari Vall d'Hebron)
Torija Recasens, Alba (Hospital Universitari Vall d'Hebron)
Jouve, Thomas (Grenoble University Hospital)
Del Bello, Arnaud (Universidad de Valladolid)
Sanz-Muñoz, Iván (Universidad de Valladolid)
Eiros, Jose Maria (Universidad de Valladolid)
Donadeu, Laura (Hospital Universitari Vall d'Hebron)
Puig-Polo, Carol (Hospital Universitari de Bellvitge)
Morandeira Rego, Francisco (Hospital Universitari de Bellvitge)
Navarro Velázquez, Sergio (Hospital Universitari de Bellvitge)
Masuet-Aumatell, Cristina (Hospital Universitari de Bellvitge)
Favà, Alexandre (Hospital Universitari de Bellvitge)
LeQuintrec, Moglie (University Hospital of Montpellier (França))
Kamar, Nassim (Grenoble University Hospital)
Crespo, Elena (Hospital Universitari Vall d'Hebron)
Bestard, Oriol (Hospital Universitari Vall d'Hebron)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad ICI14/00242 Ministerio de Economía y Competitividad PI16/01321 Instituto de Salud Carlos III PI19/01710
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Calcineurin inhibitors ; Co-stimulation blockade ; Influenza vaccination ; Kidney transplantation ; Memory B cells ; T follicular helper (Tfh) cell
Published in:	Frontiers in immunology, Vol. 13 (july 2022) , ISSN 1664-3224

DOI: 10.3389/fimmu.2022.918887
PMID: 35967428

12 p, 5.4 MB

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