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Clinical Trial
. 2016 Oct 13;128(15):1979-1986.
doi: 10.1182/blood-2016-05-719070. Epub 2016 Aug 22.

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

Raphael Carapito  1 , Nicolas Jung  2 , Marius Kwemou  2 , Meiggie Untrau  2 , Sandra Michel  1 , Angélique Pichot  2 , Gaëlle Giacometti  3 , Cécile Macquin  2 , Wassila Ilias  2 , Aurore Morlon  3 , Irina Kotova  3 , Petya Apostolova  4 , Annette Schmitt-Graeff  5 , Anne Cesbron  6 , Katia Gagne  7 , Machteld Oudshoorn  8 , Bronno van der Holt  9 , Myriam Labalette  10 , Eric Spierings  11 , Christophe Picard  12 , Pascale Loiseau  13 , Ryad Tamouza  14 , Antoine Toubert  13 , Anne Parissiadis  15 , Valérie Dubois  16 , Xavier Lafarge  17 , Myriam Maumy-Bertrand  18 , Frédéric Bertrand  18 , Luca Vago  19 , Fabio Ciceri  20 , Catherine Paillard  21 , Sergi Querol  22 , Jorge Sierra  23 , Katharina Fleischhauer  24 , Arnon Nagler  25 , Myriam Labopin  26 , Hidetoshi Inoko  27 , Peter A von dem Borne  28 , Jürgen Kuball  29 , Masao Ota  27 , Yoshihiko Katsuyama  30 , Mauricette Michallet  31 , Bruno Lioure  32 , Régis Peffault de Latour  33 , Didier Blaise  34 , Jan J Cornelissen  35 , Ibrahim Yakoub-Agha  36 , Frans Claas  37 , Philippe Moreau  38 , Noël Milpied  39 , Dominique Charron  14 , Mohamad Mohty  40 , Robert Zeiser  4 , Gérard Socié  33 , Seiamak Bahram  1
Affiliations
Clinical Trial

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

Raphael Carapito et al. Blood. .

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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Figures

Figure 1
Figure 1
Effect of MICA matching on GVHD. The cumulative incidences of grades III-IV acute GVHD (A) and chronic GVHD (B) are shown for mismatched (1) vs matched (2) patients at the MICA locus.
Figure 2
Figure 2
Effect of MICA matching on relapse and NRM. The cumulative incidence of relapse (A) and NRM (B) for mismatched (1) vs matched (2) patients at the MICA locus are shown.
Figure 3
Figure 3
Effect of MICA matching on OS. Kaplan Meier estimates of OS are shown.
See this image and copyright information in PMC

References

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