학술논문
Matching for the nonconventional MHC-I MICAgene significantly reduces the incidence of acute and chronic GVHD
Document Type
Article
Author
Carapito, Raphael; Jung, Nicolas; Kwemou, Marius; Untrau, Meiggie; Michel, Sandra; Pichot, Angélique; Giacometti, Gaëlle; Macquin, Cécile; Ilias, Wassila; Morlon, Aurore; Kotova, Irina; Apostolova, Petya; Schmitt-Graeff, Annette; Cesbron, Anne; Gagne, Katia; Oudshoorn, Machteld; van der Holt, Bronno; Labalette, Myriam; Spierings, Eric; Picard, Christophe; Loiseau, Pascale; Tamouza, Ryad; Toubert, Antoine; Parissiadis, Anne; Dubois, Valérie; Lafarge, Xavier; Maumy-Bertrand, Myriam; Bertrand, Frédéric; Vago, Luca; Ciceri, Fabio; Paillard, Catherine; Querol, Sergi; Sierra, Jorge; Fleischhauer, Katharina; Nagler, Arnon; Labopin, Myriam; Inoko, Hidetoshi; von dem Borne, Peter A.; Kuball, Jürgen; Ota, Masao; Katsuyama, Yoshihiko; Michallet, Mauricette; Lioure, Bruno; Peffault de Latour, Régis; Blaise, Didier; Cornelissen, Jan J.; Yakoub-Agha, Ibrahim; Claas, Frans; Moreau, Philippe; Milpied, Noël; Charron, Dominique; Mohty, Mohamad; Zeiser, Robert; Socié, Gérard; Bahram, Seiamak
Source
Blood; October 2016, Vol. 128 Issue: 15 p1979-1986, 8p
Subject
Language
ISSN
00064971; 15280020
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, MICAhas the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICAmismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB110/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA. MICAmismatches 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 MICAand HLA-Brenders identifying a MICA-matched donor readily feasible in clinical practice.