학술논문
Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus-host disease in conjunction with the CMV status
Document Type
Article
Author
Carapito, Raphael; Aouadi, Ismail; Pichot, Angélique; 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; Moreau, Philippe; Charron, Dominique; Mohty, Mohamad; Morishima, Yasuo; Socié, Gérard; Bahram, Seiamak
Source
Bone Marrow Transplantation; July 2020, Vol. 55 Issue: 7 p1367-1378, 12p
Subject
Language
ISSN
02683369; 14765365
Abstract
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, -DQB1and MICAloci. HLA-DPtyping was further available. MICB98mismatches 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). MICB98matching significantly reduced the effect of CMV status on overall mortality from a hazard ratio of 1.77 to 1.16. MICB98mismatches 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.