Compatibility at amino acid position 98 of MICB reduces the incidence of graft-versus-host disease in conjunction with the CMV status.

Abstract

Graft-versus-host disease (GVHD) and cytomegalovirus (CMV)-related complications are leading causes of mortality after unrelated-donor hematopoietic cell transplantation (UD-HCT). The non-conventional MHC class I gene MICB, alike MICA, encodes a stress-induced polymorphic NKG2D ligand. However, unlike MICA, MICB interacts with the CMV-encoded UL16, which sequestrates MICB intracellularly, leading to immune evasion. Here, we retrospectively analyzed the impact of mismatches in MICB amino acid position 98 (MICB98), a key polymorphic residue involved in UL16 binding, in 943 UD-HCT pairs who were allele-matched at HLA-A, -B, -C, -DRB1, -DQB1 and MICA loci. HLA-DP typing was further available. MICB98 mismatches were significantly associated with an increased incidence of acute (grade II-IV: HR, 1.20; 95% CI, 1.15 to 1.24; P < 0.001; grade III-IV: HR, 2.28; 95% CI, 1.56 to 3.34; P < 0.001) and chronic GVHD (HR, 1.21; 95% CI, 1.10 to 1.33; P < 0.001). MICB98 matching significantly reduced the effect of CMV status on overall mortality from a hazard ratio of 1.77 to 1.16. MICB98 mismatches showed a GVHD-independent association with a higher incidence of CMV infection/reactivation (HR, 1.84; 95% CI, 1.34 to 2.51; P < 0.001). Hence selecting a MICB98-matched donor significantly reduces the GVHD incidence and lowers the impact of CMV status on overall survival.

• Authors: Raphael Carapito, Ismail Aouadi, Angélique Pichot, Perrine Spinnhirny, Aurore Morlon, Irina Kotova, Cécile Macquin, Véronique Rolli, Anne Cesbron, Katia Gagne, Machteld Oudshoorn, Bronno van der Holt, Myriam Labalette, Eric Spierings, Christophe Picard, Pascale Loiseau, Ryad Tamouza, Antoine Toubert, Anne Parissiadis, Valérie Dubois, Catherine Paillard, Myriam Maumy-Bertrand, Frédéric Bertrand, Peter A von dem Borne, Jürgen H E Kuball, Mauricette Michallet, Bruno Lioure, Régis Peffault de Latour, Didier Blaise, Jan J Cornelissen, Ibrahim Yakoub-Agha, Frans Claas, Philippe Moreau, Dominique Charron, Mohamad Mohty, Yasuo Morishima, Gérard Socié, Seiamak Bahram
• Journal: Bone marrow transplantation (Bone Marrow Transplant) Vol. 55 Issue 7 Pg. 1367-1378 (07 2020) ISSN: 1476-5365 [Electronic] England
• PMID: 32286503 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids

Topics

• Amino Acids
• Cytomegalovirus Infections (epidemiology, prevention & control)
• Graft vs Host Disease (etiology, prevention & control)
• Hematopoietic Stem Cell Transplantation (adverse effects)
• Humans
• Incidence
• Retrospective Studies