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Article Dans Une Revue Bone Marrow Transplantation Année : 2020

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

1 Equipe Plate-forme GENOMAX
2 Laboratoire d'excellence (Labex) Transplantex (Nouveaux loci d’histocompatibilité et biomarqueurs en transplantation humaine, de la découverte à l’application clinique)
3 FJ-HLA - INSERM Franco-Japanese Nextgen HLA Laboratory [Strasbourg]
4 INSERM Franco-Japanese Nextgen HLA Laboratory[Nagano]
5 Nouvel Hôpital Civil de Strasbourg
6 BIOMICA SA [Strasbourg]
7 Etablissement Français du Sang [Nantes]
8 Hôpital Edouard Herriot [CHU - HCL]
9 CRCINA-ÉQUIPE 1 - Immunobiology of Human αβ and γδ T Cells and Immunotherapeutic Applications
10 Europdonor operated by Matchis Foundation [Leiden]
11 LUMC - Leiden University Medical Center
12 Erasmus MC Cancer Institute, Rotterdam
13 Laboratoire d'Immunologie [Lille]
14 LIRIC - Lille Inflammation Research International Center - U 995
15 University Medical Center [Utrecht]
16 ADES - Anthropologie bio-culturelle, Droit, Ethique et Santé
17 EMily (UMR_S_1160 / U1160) - Ecotaxie, microenvironnement et développement lymphocytaire
18 EFS - alsace strasbourg - Etablissement Français du Sang - Grand Est
19 EFS - Etablissement français du sang - Auvergne-Rhône-Alpes
20 HUS - Les Hôpitaux Universitaires de Strasbourg
21 IRMA - Institut de Recherche Mathématique Avancée
22 HCL - Hospices Civils de Lyon
23 AP-HP - Hopital Saint-Louis [AP-HP]
24 IPC - Institut Paoli-Calmettes
25 Erasmus MC - Erasmus University Medical Center [Rotterdam]
26 INFINITE (Ex-Liric) - Institute for Translational Research in Inflammation - U 1286
27 Hôpital Hôtel-Dieu [Paris]
28 CHU Saint-Antoine [AP-HP]
29 UPMC - Université Pierre et Marie Curie - Paris 6
30 CRSA - Centre de Recherche Saint-Antoine
31 Aichi Cancer Center Research Institute

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.

Domaines

Cancer
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Dates et versions

inserm-02545513 , version 1 (17-04-2020)

Identifiants

Citer

Raphaël Carapito, Ismaïl Aouadi, Angelique Pichot, Perrine Spinnhirny, Aurore Morlon, et al.. Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus host disease in conjunction with the CMV status. Bone Marrow Transplantation, 2020, 15, Online ahead of print. ⟨10.1038/s41409-020-0886-5⟩. ⟨inserm-02545513⟩
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