Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus-host disease in conjunction with the CMV status.
Fiche publication
Date publication
avril 2020
Journal
Bone marrow transplantation
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAHRAM Siamak, Dr LIOURE Bruno, Dr CARAPITO Raphaël
Tous les auteurs :
Carapito R, Aouadi I, Pichot A, Spinnhirny P, Morlon A, Kotova I, Macquin C, Rolli V, Cesbron A, Gagne K, Oudshoorn M, van der Holt B, Labalette M, Spierings E, Picard C, Loiseau P, Tamouza R, Toubert A, Parissiadis A, Dubois V, Paillard C, Maumy-Bertrand M, Bertrand F, von dem Borne PA, Kuball JHE, Michallet M, Lioure B, Peffault de Latour R, Blaise D, Cornelissen JJ, Yakoub-Agha I, Claas F, Moreau P, Charron D, Mohty M, Morishima Y, Socié G, Bahram S
Lien Pubmed
Résumé
Graft-versus-host disease (GVHD) and cytomegalovirus (CMV)-related complications are leading causes of mortality after unrelated-donor hematopoietic cell transplantation (UD-HCT). The non-conventional MHC class I gene MICB, alike MICA, encodes a stress-induced polymorphic NKG2D ligand. However, unlike MICA, MICB interacts with the CMV-encoded UL16, which sequestrates MICB intracellularly, leading to immune evasion. Here, we retrospectively analyzed the impact of mismatches in MICB amino acid position 98 (MICB98), a key polymorphic residue involved in UL16 binding, in 943 UD-HCT pairs who were allele-matched at HLA-A, -B, -C, -DRB1, -DQB1 and MICA loci. HLA-DP typing was further available. MICB98 mismatches were significantly associated with an increased incidence of acute (grade II-IV: HR, 1.20; 95% CI, 1.15 to 1.24; P < 0.001; grade III-IV: HR, 2.28; 95% CI, 1.56 to 3.34; P < 0.001) and chronic GVHD (HR, 1.21; 95% CI, 1.10 to 1.33; P < 0.001). MICB98 matching significantly reduced the effect of CMV status on overall mortality from a hazard ratio of 1.77 to 1.16. MICB98 mismatches showed a GVHD-independent association with a higher incidence of CMV infection/reactivation (HR, 1.84; 95% CI, 1.34 to 2.51; P < 0.001). Hence selecting a MICB98-matched donor significantly reduces the GVHD incidence and lowers the impact of CMV status on overall survival.
Référence
Bone Marrow Transplant.. 2020 Apr 14;: