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

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

doi:10.1038/s41409-020-0886-5

Journal articles

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

Raphaël Carapito ^{1, 2, 3, 4, 5} Ismaïl Aouadi ^{1, 2, 3, 4} Angelique Pichot ^{1, 2, 3, 4} Perrine Spinnhirny ^{1, 2, 3, 4} Aurore Morlon ^{2, 6} Irina Kotova ^{2, 6} Cécile Macquin ^{1, 2, 3, 4} Véronique Rolli ^{1, 2, 3, 4} Anne Cesbron ^{2, 7, 8} Katia Gagne ^{9, 2, 7} Machteld Oudshoorn ^{10, 11} Bronno van der Holt ¹² Myriam Labalette ^{13, 14} Eric Spierings ¹⁵ Christophe Picard ¹⁶ Pascale Loiseau ^{2, 8, 17} Ryad Tamouza ^{2, 17} Antoine Toubert ^{2, 8, 17} Anne Parissiadis ^{8, 18} Valérie Dubois ¹⁹ Catherine Paillard ^{1, 2, 8, 20} Myriam Maumy-Bertrand ²¹ Frédéric Bertrand ²¹ Peter von Dem Borne ¹¹ Jürgen Kuball ¹⁵ Mauricette Michallet ^{8, 22} Bruno Lioure ^{8, 20} Régis Peffault de Latour ^{2, 8, 23} Didier Blaise ^{8, 24} Jan J. Cornelissen ²⁵ Ibrahim Yakoub Agha ^{8, 26} Frans H.J. Claas ¹¹ Philippe Moreau ^{8, 27} Dominique Charron ^{1, 2, 17} Mohamad Mohty ^{8, 28, 29, 30} Yasuo Morishima ³¹ Gérard Socié ^{2, 8, 20} Seiamak Bahram ^{1, 2, 3, 4, 5}

1 Inserm U1109 - Equipe Plate-forme GENOMAX

Immuno-Rhumatologie Moléculaire, Fédération Hospitalo-Universitaire OMICARE, FMTS - Fédération de Médecine Translationnelle de Strasbourg

2 LabEx Transplantex [Strasbourg]

3 FJ-HLA - INSERM Franco-Japanese Nextgen HLA Laboratory [Strasbourg]

4 INSERM Franco-Japanese Nextgen HLA Laboratory[Nagano]

5 Plateau Technique de Biologie - Pôle de Biologie - Laboratoire d’Immunologie [Nouvel Hôpital Civil, 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

CRCINA - Centre de Recherche en Cancérologie et Immunologie Nantes-Angers

10 Europdonor operated by Matchis Foundation [Leiden]

11 Leiden University Medical Center (LUMC)

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 Les Hôpitaux Universitaires de Strasbourg (HUS)

21 IRMA - Institut de Recherche Mathématique Avancée

22 HCL - Hospices Civils de Lyon

23 Hôpital Saint-Louis

24 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 Université Pierre & marie Curie

30 CR Saint-Antoine - Centre de Recherche Saint-Antoine

31 Aichi Cancer Center Research Institute

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, -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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Journal articles

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Life Sciences [q-bio] / Cancer

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