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Title: Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD.
Author: Carapito R, Jung N, Kwemou M, Untrau M, Michel S, Pichot A, Giacometti G, Macquin C, Ilias W, Morlon A, Kotova I, Apostolova P, Schmitt-Graeff A, Cesbron A, Gagne K, Oudshoorn M, van der Holt B, Labalette M, Spierings E, Picard C, Loiseau P, Tamouza R, Toubert A, Parissiadis A, Dubois V, Lafarge X, Maumy-Bertrand M, Bertrand F, Vago L, Ciceri F, Paillard C, Querol S, Sierra J, Fleischhauer K, Nagler A, Labopin M, Inoko H, von dem Borne PA, Kuball J, Ota M, Katsuyama Y, Michallet M, Lioure B, Peffault de Latour R, Blaise D, Cornelissen JJ, Yakoub-Agha I, Claas F, Moreau P, Milpied N, Charron D, Mohty M, Zeiser R, Socié G, Bahram S.
Journal: Blood; 2016 Oct 13; 128(15):1979-1986. PubMed ID: 27549307.
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.

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