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Pàgina inicial > Articles > Articles publicats > Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept |
Data: | 2022 |
Resum: | 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. |
Ajuts: | Ministerio de Economía y Competitividad ICI14/00242 Ministerio de Economía y Competitividad PI16/01321 Instituto de Salud Carlos III PI19/01710 |
Drets: | 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. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | Calcineurin inhibitors ; Co-stimulation blockade ; Influenza vaccination ; Kidney transplantation ; Memory B cells ; T follicular helper (Tfh) cell |
Publicat a: | Frontiers in immunology, Vol. 13 (july 2022) , ISSN 1664-3224 |
12 p, 5.4 MB |