Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus host disease in conjunction with the CMV status

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Carapito, Raphaël | Aouadi, Ismaïl | Pichot, Angelique | Spinnhirny, Perrine | Morlon, Aurore | Kotova, Irina | Macquin, Cécile | Rolli, Véronique | Cesbron, Anne | Gagne, Katia | Oudshoorn, Machteld | van Der Holt, Bronno | Labalette, Myriam | Spierings, Eric | Picard, Christophe | Loiseau, Pascale | Tamouza, Ryad | Toubert, Antoine | Parissiadis, Anne | Dubois, Valérie | Paillard, Catherine | Maumy-Bertrand, Myriam | Bertrand, Frédéric | von Dem Borne, Peter, A. | Kuball, Jürgen, H. E. | Michallet, Mauricette | Lioure, Bruno | Peffault de Latour, Régis | Blaise, Didier | Cornelissen, Jan J. | Yakoub Agha, Ibrahim | Claas, Frans H.J. | Moreau, Philippe | Charron, Dominique | Mohty, Mohamad | Morishima, Yasuo | Socié, Gérard | Bahram, Seiamak

Edité par CCSD ; Nature Publishing Group -

International audience. 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.

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