Donor CTLA-4 Genotype Modulates the Immune Response to Minor Histocompatibility Antigen Mismatches
Por:
Gallardo, D, Bosch-Vizcaya, A, Rodriguez-Romanos, R, Santos, N, Buno, I, de la Camara, R, Brunet, S, Jimenez-Velasco, A, Gonzalez, M, Nieto, JB, Martinez-Laperche, C, Vallejo, C, Ferra, C, Sampol, A, Lopez-Jimenez, J, Perez-Simon, JA, Martinez, C, Diez, JL
Publicada:
1 dic 2017
Resumen:
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. (C) 2017 American Society for Blood and Marrow Transplantation.
Filiaciones:
Gallardo, D:
Hosp Dr Josep Trueta, IDIBGI, Inst Catala Oncol, Hematol Dept, Girona, Spain
Bosch-Vizcaya, A:
Hosp Dr Josep Trueta, IDIBGI, Inst Catala Oncol, Hematol Dept, Girona, Spain
Rodriguez-Romanos, R:
Hosp Dr Josep Trueta, IDIBGI, Inst Catala Oncol, Hematol Dept, Girona, Spain
Santos, N:
Hosp Dr Josep Trueta, IDIBGI, Inst Catala Oncol, Hematol Dept, Girona, Spain
Buno, I:
Hosp Gregorio Maranon, Hematol Dept, Madrid, Spain
de la Camara, R:
Hosp La Princesa, Hematol Dept, Madrid, Spain
Brunet, S:
Hosp Santa Creu & Sant Pau, Hematol Dept, Barcelona, Spain
Jimenez-Velasco, A:
Hosp Reg Univ, Hematol Dept, Malaga, Spain
Gonzalez, M:
Hosp Univ, Hematol Dept, Salamanca, Spain
Nieto, JB:
Hosp Morales Meseguer, Hematol Dept, Murcia, Spain
Martinez-Laperche, C:
Hosp Gregorio Maranon, Hematol Dept, Madrid, Spain
Vallejo, C:
Hosp Univ Donostia, Hematol Dept, San Sebastian, Spain
Ferra, C:
Hosp Badalona Germans Trias & Pujol, Inst Catala Oncol, Hematol Dept, Badalona, Spain
Sampol, A:
Hosp Son Espases, Hematol Dept, Palma De Mallorca, Spain
Lopez-Jimenez, J:
Hosp Ramon & Cajal, Hematol Dept, Madrid, Spain
Perez-Simon, JA:
Hosp Virgen Rocio, Hematol Dept, Seville, Spain
Martinez, C:
Hosp Clin Barcelona, Hematol Dept, Barcelona, Spain
Diez, JL:
Hosp Gregorio Maranon, Hematol Dept, Madrid, Spain
Hybrid Gold
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