Donor CTLA-4 Genotype Modulates the Immune Response to Minor Histocompatibility Antigen Mismatches

Minor histocompatibility antigen (miHA) mismatches have been related to graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, but this association remains controversial due to the lack of consistency in the results obtained by different groups. The CTLA-4 genotype of the donor...

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Detalles Bibliográficos
Autores: Gallardo, David, Bosch-Vizcaya, Anna, Rodriguez-Romanos, Rocio, Santos, Nazly, Buno, Ismael, de la Cámara, Rafael, Brunet, Salut, Jimenez-Velasco, Antonio, Gonzalez, Marcos, Nieto, Jose B, Martinez-Laperche, Carolina, Vallejo, Carlos, Ferra, Christelle, Sampol Mayol, Antonia, Lopez-Jimenez, Javier, Perez-Simon, Jose A, Martinez, Carmen, Diez, Jose-Luis, Spanish Hematopoietic Transplant
Tipo de recurso: artículo
Fecha de publicación:2017
País:España
Institución:Instituto de Salud Carlos III (ISCIII)
Repositorio:Repisalud
Idioma:inglés
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/20386
Acceso en línea:http://hdl.handle.net/20.500.12105/20386
Access Level:acceso abierto
Palabra clave:CTLA-4
Minor histocompatibility antigens
Graft-versus-host disease
Allogeneic transplantation
Antígenos de Histocompatibilidad Menor
Enfermedad Injerto contra Huésped
Donantes de Tejidos
Lactante
Adolescente
Inmunidad
Preescolar
Histocompatibilidad
Humanos
Persona de Mediana Edad
Adulto Joven
Anciano
Genotipo
Niño
Adulto
Antígeno CTLA-4
Child
Genotype
Aged
CTLA-4 Antigen
Young Adult
Adult
Histocompatibility
Humans
Immunity
Child, Preschool
Adolescent
Middle Aged
Infant
Graft vs Host Disease
Tissue Donors
Minor Histocompatibility Antigens
Descripción
Sumario:Minor histocompatibility antigen (miHA) mismatches have been related to graft-versus-host disease (GVHD) after allogeneic stem cell transplantation, but this association remains controversial due to the lack of consistency in the results obtained by different groups. The CTLA-4 genotype of the donor has been reported to be relevant in the appearance of acute GVHD. We explored the effect of the donor's CTLA-4 genotype in the incidence of acute GVHD associated with HA-1, HA-8, or H-Y miHA mismatches in a large cohort of 1295 patients receiving an allogeneic transplant from an HLA-identical sibling donor. The incidence of acute GVHD was higher if the donor and recipient were mismatched for HA-1, HA-8, or H-Y, but only when the donor had the CTLA-4 rs231775 AA genotype (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.27 to 3.75; P=.005; HR, 2.11, 95% CI, 1.06 to 4.18; P=.033; and HR, 1.50; 95% CI, 1.05 to 2.15; P=.025, respectively). In contrast, this increased risk of developing acute GVHD was not found when the donor presented the CTLA-4 rs231775 AG or GG genotypes. We conclude that the immune response to specific miHA mismatches is modulated by the CTLA-4 genotype of the donor.

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