Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

Raphael Carapito, Nicolas Jung, Marius Kwemou, Meiggie Untrau, Sandra Michel, Angélique Pichot, Gaëlle Giacometti, Cécile Macquin, Wassila Ilias, Aurore Morlon, Irina Kotova, Petya Apostolova, Annette Schmitt-Graeff, Anne Cesbron, Katia Gagne, Machteld Oudshoorn, Bronno Van Der Holt, Myriam Labalette, Eric Spierings, Christophe PicardPascale Loiseau, Ryad Tamouza, Antoine Toubert, Anne Parissiadis, Valérie Dubois, Xavier Lafarge, Myriam Maumy-Bertrand, Frédéric Bertrand, Luca Vago, Fabio Ciceri, Catherine Paillard, Sergi Querol, Jorge Sierra, Katharina Fleischhauer, Arnon Nagler, Myriam Labopin, Hidetoshi Inoko, Peter A. Von Dem Borne, Jürgen Kuball, Masao Ota, Yoshihiko Katsuyama, Mauricette Michallet, Bruno Lioure, Régis Peffault De Latour, Didier Blaise, Jan J. Cornelissen, Ibrahim Yakoub-Agha, Frans Claas, Philippe Moreau, Noël Milpied, Dominique Charron, Mohamad Mohty, Robert Zeiser, Gérard Socié, Seiamak Bahram

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35 Citations (Scopus)

Abstract

© 2016 by The American Society of Hematology. 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.
Original languageEnglish
Pages (from-to)1979-1986
JournalBlood
Volume128
Issue number15
DOIs
Publication statusPublished - 13 Oct 2016

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