Impact of donor NKG2D and MICA gene polymorphism on clinical outcomes of adult and paediatric allogeneic cord blood transplantation for malignant diseases

• Published in: European journal of haematology Vol. 113; no. 1; pp. 32 - 43
• Main Authors: Cox, Steven T., Patterson, Warren, Duggleby, Richard, Jones, Owen J. R., Madrigal, J. Alejandro, Querol, Sergi, Salvador, Francesc Rudilla, Mata, Maria Jose Herrero, Volt, Fernanda, Gluckman, Éliane, Szydlo, Richard, Danby, Robert D., Hernandez, Diana
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.07.2024
• Subjects: Adolescent; Adult; Aged; Alleles; Allografts; bone marrow; CD8 antigen; Cell activation; Child; Child, Preschool; Cord blood; Cord Blood Stem Cell Transplantation; Female; fetal blood; Gene polymorphism; Genotype; Graft Survival; Graft vs Host Disease - etiology; Graft vs Host Disease - genetics; haematopoietic stem cell; haplotype; Hematopoietic Stem Cell Transplantation - methods; Hematopoietic stem cells; Histocompatibility Antigens Class I - genetics; Humans; Infant; killer cells; Leukocytes (neutrophilic); Ligands; Lymphocytes T; Male; Methionine; MICA protein; Middle Aged; Multivariate analysis; natural; Natural killer cells; Neoplasms - genetics; Neoplasms - therapy; NK Cell Lectin-Like Receptor Subfamily K - genetics; NKG2D; Pediatrics; Polymorphism; Polymorphism, Genetic; Retrospective Studies; Tissue Donors; Transplantation, Homologous; Transplants & implants; Treatment Outcome; Valine; Young Adult; NKG2D; haplotype; natural; fetal blood; bone marrow; haematopoietic stem cell; killer cells; genotype
• ISSN: 0902-4441; 1600-0609; 1600-0609
• DOI: 10.1111/ejh.14202

Objectives NKG2D is an activating receptor expressed by natural killer (NK) and CD8+ T cells and activation intensity varies by NKG2D expression level or nature of its ligand. An NKG2D gene polymorphism determines high (HNK1) or low (LNK1) expression. MICA is the most polymorphic NKG2D ligand and stronger effector cell activation associates with methionine rather than valine at residue 129. We investigated correlation between cord blood (CB) NKG2D and MICA genotypes and haematopoietic stem cell (HSC) transplant outcome. Methods We retrospectively studied 267 CB HSC recipients (178 adult and 87 paediatric) who underwent transplant for malignant disease between 2007 and 2018, analysing CB graft DNA for NKG2D and MICA polymorphisms using Sanger sequencing. Multivariate analysis was used to correlate these results with transplant outcomes. Results In adult patients, LNK1 homozygous CB significantly improved 60‐day neutrophil engraftment (hazard ratio (HR) 0.6; 95% confidence interval (CI) 0.4–0.9; p = .003). In paediatrics, HNK1 homozygous CB improved 60‐day engraftment (HR 0.4; 95% CI 0.2–0.7; p = .003), as did MICA‐129 methionine+ CB grafts (HR 1.7 95% CI 1.1–2.6; p = .02). Conclusion CB NKG2D and MICA genotypes potentially improve CB HSC engraftment. However, results contrast between adult and paediatric recipients and may reflect transplant procedure disparities between cohorts.