title: Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD.
abstract: Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain-related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA MICA mismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P < .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P < .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P < .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P < .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice.
authors.affiliation: Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM Unité Mixte de Recherche (UMR)_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, and LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France; Laboratoire d'Immunologie, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Strasbourg, France.
authors.forename: Raphael
authors.initials: R
authors.lastname: Carapito
authors.affiliation: Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM Unité Mixte de Recherche (UMR)_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, and LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Jung
authors.affiliation: Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM Unité Mixte de Recherche (UMR)_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, and LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France.
authors.forename: Marius
authors.initials: M
authors.lastname: Kwemou
authors.affiliation: Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM Unité Mixte de Recherche (UMR)_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, and LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France.
authors.forename: Meiggie
authors.initials: M
authors.lastname: Untrau
authors.affiliation: Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM Unité Mixte de Recherche (UMR)_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, and LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France; Laboratoire d'Immunologie, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Strasbourg, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Michel
authors.affiliation: Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM Unité Mixte de Recherche (UMR)_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, and LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France.
authors.forename: Angélique
authors.initials: A
authors.lastname: Pichot
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; BIOMICA SAS, Strasbourg, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Giacometti
authors.affiliation: Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM Unité Mixte de Recherche (UMR)_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, and LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Macquin
authors.affiliation: Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM Unité Mixte de Recherche (UMR)_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, and LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France.
authors.forename: Wassila
authors.initials: W
authors.lastname: Ilias
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; BIOMICA SAS, Strasbourg, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Morlon
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; BIOMICA SAS, Strasbourg, France.
authors.forename: Irina
authors.initials: I
authors.lastname: Kotova
authors.affiliation: Department of Hematology and Oncology, Freiburg University Medical Center, Centre for Biological Signalling Studies BIOSS, Albert Ludwigs University, Freiburg, Germany.
authors.forename: Petya
authors.initials: P
authors.lastname: Apostolova
authors.affiliation: Institute of Pathology, University Hospital, Freiburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Schmitt-Graeff
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; Etablissement Français du Sang (EFS) Pays de la Loire, Laboratoire HLA, Nantes, France; Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Société Francophone d'Histocompatibilité et d'Immunogénétique, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Cesbron
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; Etablissement Français du Sang (EFS) Pays de la Loire, Laboratoire HLA, Nantes, France; Laboratoire EA4271 "Immunovirologie et Polymorphisme Génétique," Nantes, France.
authors.forename: Katia
authors.initials: K
authors.lastname: Gagne
authors.affiliation: Europdonor, Matchis Foundation, Leiden, The Netherlands; Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Machteld
authors.initials: M
authors.lastname: Oudshoorn
authors.affiliation: Haemato Oncology Foundation for Adults in the Netherlands Data Center, Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.affiliation: Laboratoire d'Immunologie, Centre Hospitalier Régional Universitaire de Lille, Lille, France; Lille Inflammation Research International Center INSERM U995, Université Lille 2, Lille, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labalette
authors.affiliation: Laboratory for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Eric
authors.initials: E
authors.lastname: Spierings
authors.affiliation: Aix-Marseille Université, Centre National de la Recherche Scientifique (CNRS), EFS, Anthropologie bio-culturelle, Droit, Éthique & Santé UMR 7268, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Picard
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Laboratoire Jean Dausset, INSERM UMR_S 1160, Hôpital Saint-Louis, Paris, France.
authors.forename: Pascale
authors.initials: P
authors.lastname: Loiseau
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; Laboratoire Jean Dausset, INSERM UMR_S 1160, Hôpital Saint-Louis, Paris, France.
authors.forename: Ryad
authors.initials: R
authors.lastname: Tamouza
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Laboratoire Jean Dausset, INSERM UMR_S 1160, Hôpital Saint-Louis, Paris, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Toubert
authors.affiliation: Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; EFS Alsace Lorraine Champagne Ardenne, Laboratoire HLA, Strasbourg, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Parissiadis
authors.affiliation: EFS Rhône-Alpes, Laboratoire HLA, Lyon, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Dubois
authors.affiliation: EFS Aquitaine Limousin, Laboratoire HLA, Bordeaux, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Lafarge
authors.affiliation: Institut de Recherche Mathématique Avancée, CNRS UMR 7501, LabEx Institut de Recherche en Mathématiques, ses Interactions et Applications, Université de Strasbourg, Strasbourg, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Maumy-Bertrand
authors.affiliation: Institut de Recherche Mathématique Avancée, CNRS UMR 7501, LabEx Institut de Recherche en Mathématiques, ses Interactions et Applications, Université de Strasbourg, Strasbourg, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bertrand
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, and Unit of Immunogenetics, Leukemia Genomics, and Immunobiology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Vago
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, and.
authors.forename: Fabio
authors.initials: F
authors.lastname: Ciceri
authors.affiliation: Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM Unité Mixte de Recherche (UMR)_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, and LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Service d'Hématologie et d'Oncologie pédiatrique, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Paillard
authors.affiliation: Barcelona Cord Blood Bank, Barcelona, Spain.
authors.forename: Sergi
authors.initials: S
authors.lastname: Querol
authors.affiliation: Hematology Department, Hospital de la Santa Creu I Sant Pau, IIB Sant Pau and Josep Carreras Leukemia Research Institute, Universitat Autònoma de Barcelona, Red de Càncer, Barcelona, Spain.
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
authors.affiliation: Institute of Experimental Cellular Therapy, Essen University Hospital, Essen, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Fleischhauer
authors.affiliation: Chaim Sheba Medical Center, Tel Aviv University, Tel-Hashomer, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Nagler
authors.affiliation: Département d'Hématologie, Hôpital Saint Antoine, Paris, France.
authors.forename: Myriam
authors.initials: M
authors.lastname: Labopin
authors.affiliation: INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France; Department of Legal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Inoko
authors.affiliation: Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Peter A
authors.initials: PA
authors.lastname: von dem Borne
authors.affiliation: Department of Hematology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kuball
authors.affiliation: INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France; Department of Legal Medicine, Shinshu University School of Medicine, Matsumoto, Nagano, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Ota
authors.affiliation: INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France; Department of Pharmacy, Shinshu University Hospital, Matsumoto, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Katsuyama
authors.affiliation: Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Centre Hospitalier Lyon Sud, Hématologie 1G, Hospices Civils de Lyon, Pierre Bénite, Lyon, France.
authors.forename: Mauricette
authors.initials: M
authors.lastname: Michallet
authors.affiliation: Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Service d'Hématologie Adulte, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Lioure
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Service d'Hématologie-Greffe, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Régis
authors.initials: R
authors.lastname: Peffault de Latour
authors.affiliation: Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Institut Paoli Calmettes, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Blaise
authors.affiliation: Department of Hematology and Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Cornelissen
authors.affiliation: Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Lille Inflammation Research International Center INSERM U995, Université Lille 2, Lille, France.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yakoub-Agha
authors.affiliation: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Claas
authors.affiliation: Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Service d'Hématologie Clinique, CHU Hôtel Dieu, Nantes, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.affiliation: Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Service d'Hématologie et de Thérapie Cellulaire, CHU Haut-Lévêque, Bordeaux, France.
authors.forename: Noël
authors.initials: N
authors.lastname: Milpied
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; Laboratoire Jean Dausset, INSERM UMR_S 1160, Hôpital Saint-Louis, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Charron
authors.affiliation: Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Département d'Hématologie, Hôpital Saint Antoine, Paris, France; Université Pierre & Marie Curie, Paris, France; and Centre de Recherche Saint-Antoine, INSERM UMR_S 938, Paris, France.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mohty
authors.affiliation: Department of Hematology and Oncology, Freiburg University Medical Center, Centre for Biological Signalling Studies BIOSS, Albert Ludwigs University, Freiburg, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Zeiser
authors.affiliation: LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; Société Francophone de Greffe de Moelle et de Thérapie Cellulaire, Hôpital Edouard Herriot, Centre Hospitalier Universitaire (CHU), Lyon, France; Service d'Hématologie-Greffe, Hôpital Saint-Louis, Assistance Publique-Hôpitaux de Paris, Paris, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Socié
authors.affiliation: Laboratoire d'ImmunoRhumatologie Moléculaire, INSERM Unité Mixte de Recherche (UMR)_S1109, Plateforme GENOMAX, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, and LabEx TRANSPLANTEX, Faculté de Médecine, Université de Strasbourg, Strasbourg, France; INSERM Franco-Japanese Nextgen HLA laboratory, Nagano, Japan and Strasbourg, France; Laboratoire d'Immunologie, Plateau Technique de Biologie, Pôle de Biologie, Nouvel Hôpital Civil, Strasbourg, France.
authors.forename: Seiamak
authors.initials: S
authors.lastname: Bahram
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D006680:HLA Antigens / Q000235:genetics*; D018380:Hematopoietic Stem Cell Transplantation; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics; D012189:Retrospective Studies
chemical_list: D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D055655:NK Cell Lectin-Like Receptor Subfamily K