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

_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. Access through your institution Buy or subscribe This is a preview of

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DISPARITY ON REDUCED-INTENSITY-CONDITIONED ALLOGENEIC STEM CELL TRANSPLANTS FROM HLA MISMATCHED UNRELATED DONORS FOR AML: FROM THE ALWP OF THE EBMT Article 02 October 2020 THE OUTCOME OF TWO

OR MORE HLA LOCI MISMATCHED UNRELATED DONOR HEMATOPOIETIC CELL TRANSPLANTATION FOR ACUTE LEUKEMIA: AN ALWP OF THE EBMT STUDY Article 19 June 2020 INDIVIDUAL HLAS INFLUENCE IMMUNOLOGICAL

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Scholar  Download references ACKNOWLEDGEMENTS We would like to thank Prof. Robert Zeiser (University of Freiburg/Germany) for critical reading of this manuscript. We thank Martin Verniquet

for critical review of statistical analyses. We would also like to thank Nicole Raus (SFGM-TC, Lyon, France) for retrieving the clinical data from the ProMISe database. This work was

supported by grants from the Agence Nationale de la Recherche (ANR) (ANR-11-LABX-0070_TRANSPLANTEX), and the INSERM (UMR_S 1109), the Institut Universitaire de France (IUF), all to SB; from

the University of Strasbourg (IDEX UNISTRA) to CP and SB; from the European regional development fund (European Union) INTERREG V program (project n°3.2 TRIDIAG) to RC and SB; and from

MSD-Avenir grant AUTOGEN to SB. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Laboratoire d’ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, Plateforme GENOMAX, Faculté de Médecine,

Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France Raphael Carapito, Ismail Aouadi, 

Angélique Pichot, Perrine Spinnhirny, Cécile Macquin, Véronique Rolli, Catherine Paillard, Dominique Charron & Seiamak Bahram * Labex TRANSPLANTEX, Faculté de Médecine, Université de

Strasbourg, Strasbourg, France Raphael Carapito, Ismail Aouadi, Angélique Pichot, Perrine Spinnhirny, Aurore Morlon, Irina Kotova, Cécile Macquin, Véronique Rolli, Anne Cesbron, Katia Gagne,

 Pascale Loiseau, Ryad Tamouza, Antoine Toubert, Catherine Paillard, Régis Peffault de Latour, Dominique Charron, Gérard Socié & Seiamak Bahram * INSERM Franco-Japanese Nextgen HLA

Laboratory, Strasbourg, France Raphael Carapito, Ismail Aouadi, Angélique Pichot, Perrine Spinnhirny, Cécile Macquin, Véronique Rolli & Seiamak Bahram * INSERM Franco-Japanese Nextgen

HLA Laboratory, Nagano, Japan Raphael Carapito, Ismail Aouadi, Angélique Pichot, Perrine Spinnhirny, Cécile Macquin, Véronique Rolli & Seiamak Bahram * Laboratoire d’Immunologie, Plateau

Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Strasbourg, France Raphael Carapito & Seiamak Bahram * BIOMICA SAS, Strasbourg, France Aurore Morlon & Irina Kotova *

Etablissement Français du Sang (EFS) Centre-Pays de la Loire, Laboratoire HLA, Nantes, France Anne Cesbron & Katia Gagne * Société Francophone de Greffe de Moelle et de Thérapie

Cellulaire (SFGM-TC), Hôpital Edouard Herriot, CHU, Lyon, France Anne Cesbron, Pascale Loiseau, Antoine Toubert, Anne Parissiadis, Catherine Paillard, Mauricette Michallet, Bruno Lioure, 

Régis Peffault de Latour, Didier Blaise, Ibrahim Yakoub-Agha, Philippe Moreau, Mohamad Mohty & Gérard Socié * Société Francophone d’Histocompatibilité et d’Immunogénétique (SFHI), Paris,

France Anne Cesbron * INSERM 1232, CRCINA, Université Nantes-Angers, Nantes, France Katia Gagne * Europdonor operated by Matchis Foundation, Leiden, The Netherlands Machteld Oudshoorn *

Department of Immunohematology and Blood transfusion, LUMC, Leiden, The Netherlands Machteld Oudshoorn & Frans Claas * HOVON Data Center, Department of Hematology, Erasmus MC Cancer

Institute, Rotterdam, The Netherlands Bronno van der Holt * Laboratoire d’Immunologie, CHRU de Lille, Lille, France Myriam Labalette * LIRIC INSERM U995, Université Lille 2, Lille, France

Myriam Labalette & Ibrahim Yakoub-Agha * Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands Eric Spierings * CNRS, EFS-PACA, ADES UMR

7268, Aix-Marseille Université, Marseille, France Christophe Picard * Laboratoire Jean Dausset, INSERM UMR_S 1160, Hôpital Saint-Louis, Paris, France Pascale Loiseau, Ryad Tamouza, Antoine

Toubert & Dominique Charron * Etablissement Français du Sang (EFS) Grand-Est, Laboratoire HLA, Strasbourg, France Anne Parissiadis * Etablissement Français du Sang (EFS) Rhône-Alpes,

Laboratoire HLA, Lyon, France Valérie Dubois * Service d’Hématologie et d’Oncologie pédiatrique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France Catherine Paillard * Institut de

Recherche Mathématique Avancée, CNRS UMR 7501, LabEx Institut de Recherche en Mathématiques, ses Interactions et Applications, Université de Strasbourg, Strasbourg, France Myriam

Maumy-Bertrand & Frédéric Bertrand * Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands Peter A. von dem Borne * Department of Hematology, University

Medical Center Utrecht, Utrecht, The Netherlands Jürgen H. E. Kuball * Centre Hospitalier Lyon Sud, Hématologie 1G, Hospices Civils de Lyon, Pierre Bénite, Lyon, France Mauricette Michallet

* Service d’Hématologie Adulte, Hôpitaux Universitaires de Strasbourg, Strasbourg, France Bruno Lioure & Gérard Socié * Service d’Hématologie – Greffe, Hôpital Saint-Louis, APHP, Paris,

France Régis Peffault de Latour * Institut Paoli Calmettes, Marseille, France Didier Blaise * Department of Hematology and ErasmusMC Cancer Institute, Erasmus University Medical Center,

Rotterdam, The Netherlands Jan J. Cornelissen * Service d’Hématologie Clinique, CHU Hôtel Dieu, Nantes, France Philippe Moreau * Département d’Hématologie, Hôpital Saint Antoine, Paris,

France Mohamad Mohty * Université Pierre & Marie Curie, Paris, France Mohamad Mohty * Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Paris, France Mohamad Mohty * Division of

Epidemiology and Prevention, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Japan Yasuo Morishima Authors * Raphael Carapito View author publications You can also

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inPubMed Google Scholar * Yasuo Morishima View author publications You can also search for this author inPubMed Google Scholar * Gérard Socié View author publications You can also search for

this author inPubMed Google Scholar * Seiamak Bahram View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS RC performed the experiments,

designed the study, analyzed the data, and wrote the manuscript. SB designed the study, analyzed the data and wrote the manuscript. PS, AM, IK, CM, APi, and VR performed the experiments and

analyzed the data. IA performed the statistics. PAB, DB, AC, DC, FC, KG, JK, JC, ML, PL, MMi, PM, MOu, APa, RPL, CPi, GS, ES, RT, AT, IY, VD and BH provided samples and clinical data,

interpreted the clinical data and discussed the results. BL, MMo, AN, YM and CPa interpreted the clinical data and discussed results. FB, MMB, and BH analyzed the data and reviewed

statistics. All authors contributed to the writing of the report and approved the final version of the manuscript. CORRESPONDING AUTHORS Correspondence to Raphael Carapito or Seiamak Bahram.

ETHICS DECLARATIONS CONFLICT OF INTEREST SB is the scientific founder and a (minority) shareholder of BIOMICA SAS. JK is the co-founder and chief scientific officer of Gadeta. He received

personal fees from Gadeta. In addition, JK has a patent issued/pending. ES is the inventor of a patent application filed by the University Medical Center Utrecht on the prediction of an

alloimmune response against mismatched HLA (PCT/EPT2013/073386). All other authors declare no conflict of interests. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral

with regard to jurisdictional claims in published maps and institutional affiliations. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TABLE 1 FIGURE S1 FIGURE S1. LEGEND RIGHTS AND PERMISSIONS

Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Carapito, R., Aouadi, I., Pichot, A. _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 Transplant_ 55, 1367–1378 (2020). https://doi.org/10.1038/s41409-020-0886-5 Download citation * Received: 17

December 2019 * Revised: 17 March 2020 * Accepted: 23 March 2020 * Published: 14 April 2020 * Issue Date: July 2020 * DOI: https://doi.org/10.1038/s41409-020-0886-5 SHARE THIS ARTICLE Anyone

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