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Carapito, R.; Aouadi, I.; Pichot, A.; Spinnhirny, P.; Morlon, A.; Kotova, I.; ... ; Bahram, S. (2020)

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

Article / Letter to editor
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...Show moreGraft-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.Show less
All authors
Carapito, R.; Aouadi, I.; Pichot, A.; Spinnhirny, P.; Morlon, A.; Kotova, I.; Macquin, C.; Rolli, V.; Cesbron, A.; Gagne, K.; Oudshoorn, M.; Holt, B. van der; Labalette, M.; Spierings, E.; Picard, C.; Loiseau, P.; Tamouza, R.; Toubert, A.; Parissiadis, A.; Dubois, V.; Paillard, C.; Maumy-Bertrand, M.; Bertrand, F.; Borne, P.A. von dem; Kuball, J.H.E.; Michallet, M.; Lioure, B.; Latour, R.P. de; Blaise, D.; Cornelissen, J.J.; Yakoub-Agha, I.; Claas, F.; Moreau, P.; Charron, D.; Mohty, M.; Morishima, Y.; Socie, G.; Bahram, S.
Date
2020-04-14
Journal
Bone Marrow Transplantation
Volume
55
Issue
7
Pages
1367 - 1378
DOI
doi:10.1038/s41409-020-0886-5
Link
https://www.nature.com/articles/s41409-020-0886-5