TY - JOUR
T1 - Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD
AU - Carapito, Raphael
AU - Jung, Nicolas
AU - Kwemou, Marius
AU - Untrau, Meiggie
AU - Michel, Sandra
AU - Pichot, Angélique
AU - Giacometti, Gaëlle
AU - Macquin, Cécile
AU - Ilias, Wassila
AU - Morlon, Aurore
AU - Kotova, Irina
AU - Apostolova, Petya
AU - Schmitt-Graeff, Annette
AU - Cesbron, Anne
AU - Gagne, Katia
AU - Oudshoorn, Machteld
AU - Van Der Holt, Bronno
AU - Labalette, Myriam
AU - Spierings, Eric
AU - Picard, Christophe
AU - Loiseau, Pascale
AU - Tamouza, Ryad
AU - Toubert, Antoine
AU - Parissiadis, Anne
AU - Dubois, Valérie
AU - Lafarge, Xavier
AU - Maumy-Bertrand, Myriam
AU - Bertrand, Frédéric
AU - Vago, Luca
AU - Ciceri, Fabio
AU - Paillard, Catherine
AU - Querol, Sergi
AU - Sierra, Jorge
AU - Fleischhauer, Katharina
AU - Nagler, Arnon
AU - Labopin, Myriam
AU - Inoko, Hidetoshi
AU - Von Dem Borne, Peter A.
AU - Kuball, Jürgen
AU - Ota, Masao
AU - Katsuyama, Yoshihiko
AU - Michallet, Mauricette
AU - Lioure, Bruno
AU - De Latour, Régis Peffault
AU - Blaise, Didier
AU - Cornelissen, Jan J.
AU - Yakoub-Agha, Ibrahim
AU - Claas, Frans
AU - Moreau, Philippe
AU - Milpied, Noël
AU - Charron, Dominique
AU - Mohty, Mohamad
AU - Zeiser, Robert
AU - Socié, Gérard
AU - Bahram, Seiamak
PY - 2016/10/13
Y1 - 2016/10/13
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2016-05-719070
DO - 10.1182/blood-2016-05-719070
M3 - Article
AN - SCOPUS:84991696074
VL - 128
SP - 1979
EP - 1986
JO - Blood
JF - Blood
SN - 0006-4971
IS - 15
ER -