Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus-host disease in conjunction with the CMV status
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
(2020) Bone Marrow Transplantation, volume 55, issue 7, pp. 1367 - 1378
(Article)
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.
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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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Keywords: Transplantation, Hematology, Journal Article
ISSN: 0268-3369
Publisher: Nature Publishing Group
Note: Publisher Copyright: © 2020, The Author(s), under exclusive licence to Springer Nature Limited.
(Peer reviewed)