Impaired antigen-specific B-cell responses after Influenza vaccination in kidney transplant recipients receiving co-stimulation blockade with Belatacept

Autor: 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 Aumatell, Cristina, Favà, Alexandre, Lequintrec, Moglie, Kamar, Nassim, Crespo, Elena, Bestard Matamoros, Oriol
Přispěvatelé: Institut Català de la Salut, [Pernin V] Kidney Transplant Unit, Nephrology Department. Montpellier University Hospital, Montpellier, France. [Meneghini M, Bestard O] Unitat de Trasplantament Renal, Servei de Nefrologia, Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Laboratori de Nefrologia i Trasplantament Renal, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Torija A, Donadeu L, Polo C] Laboratori de Nefrologia i Trasplantament Renal, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. [Jouve T] Laboratori de Nefrologia i Trasplantament Renal, Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. Kidney transplant Unit, Nephrology Department. Grenoble University Hospital, Grenoble, France. [Del Bello A] Centro Nacional de Gripe de Valladolid, Universidad de Valladolid, Valladolid, Spain. [Sanz-Muñoz I] Centro Nacional de Gripe, Valladolid Universidad de Valladolid, Valladolid, Spain, Vall d'Hebron Barcelona Hospital Campus
Rok vydání: 2022
Předmět:
sistemas sanguíneo e inmunológico::sangre::células sanguíneas::leucocitos::leucocitos mononucleares::linfocitos::sistemas sanguíneo e inmunológico::sistemas sanguíneo e inmunológico::linfocitos B [ANATOMÍA]
Complex Mixtures::Biological Products::Vaccines::Viral Vaccines::Influenza Vaccines [CHEMICALS AND DRUGS]
Cèl·lules B
Ronyons - Trasplantació
Immunology
Vaccination
Trasplantament renal
Influenzavirus
Kidney Transplantation
Transplant Recipients
Virus de la gripe
Kidney transplantation
Persons::Transplant Recipients [NAMED GROUPS]
Abatacept
Influenza A Virus
H1N1 Subtype
mezclas complejas::productos biológicos::vacunas::vacunas víricas::vacunas de la gripe [COMPUESTOS QUÍMICOS Y DROGAS]
Hemic and Immune Systems::Blood::Blood Cells::Leukocytes::Leukocytes
Mononuclear::Lymphocytes::Hemic and Immune Systems::Hemic and Immune Systems::B-Lymphocytes [ANATOMY]
Immunology and Allergy
Humans
Vacunes antigripals
personas::receptores de trasplantes [DENOMINACIONES DE GRUPOS]
Zdroj: Dipòsit Digital de la UB
Universidad de Barcelona
Scientia
ISSN: 1664-3224
Popis: Inhibidores de la calcineurina; Vacunación antigripal; Trasplante de riñón Calcineurin inhibitors; Influenza vaccination; Kidney transplantation Inhibidors de la calcineurina; Vacunació antigripal; Trasplantament de ronyó 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. This work was supported by the Instituto de Salud Carlos III (ISCIII) (grant numbers ICI14/00242 and PI16/01321, PI19/01710) and by the European Union’s Horizon 2020 Research and innovation program (grant agreement 754995). Also, this work was partly supported by the SLT002/16/00183 grant, from the Department of Health of the Generalitat de Catalunya by the call “Accioí instrumental de programes derecerca orientats en l’àmbit de la recerca i la innovacioí en salut.” The authors thank the Research Centers of Catalonia (CERCA) Programme/Generalitat de Catalunya for institutional support. OB was awarded with an intensification grant from the “Instituto de Salud Carlos III” [INT19/00051].
Databáze: OpenAIRE
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