The impact of donor full-length KIR2DS4 in the development of acute and chronic GVHD after unrelated allogeneic HSCT

Pediatr Transplant. 2020 Sep;24(6):e13728. doi: 10.1111/petr.13728. Epub 2020 Jun 27.

Abstract

Background: Killer Ig-like receptor 2DS4 (KIR2DS4) is the most prevalent activating killer Ig-like receptor gene. It is divergent and encodes either full-length or deleted allele variants. The studies of donor killer KIR2DS4 in unrelated allogeneic hematopoietic stem cell transplantations were limited.

Methods: KIR and HLA genotyping were determined in 75 pairs of Chinese pediatric hematologic malignancy patients.

Results: Among the 75 donor-recipient pairs, 77.3% (58/75) of the donors were positive for full-length KIR2DS4 and 22.7% (17/75) were negative. Patients who had donors positive for full-length KIR2DS4 had higher cumulative incidence of aGVHD than patients whose donor negative for full-length KIR2DS4 (86.2% versus 76.5%, P = .038). Multivariate analysis showed full-length KIR2DS4 was the significant factor for I-IV aGVHD (HR = 2.166, 95% CI: 1.01-4.26, P = .025). Subgroup analysis showed that AML and CML patients who received donors negative for full-length KIR2DS4 have a higher cumulative incidences of cGVHD (75% vs 62%, P = .008). There were no significant effects of full-length KIR2DS4 on overall survival (P = .13), relapse-free survival (P = .14), CMV reactivation (P = .52), and relapse (HR = 0.38, 95% CI: 0.09-1.6, P = .1875).

Conclusions: Our findings indicated a significant correlation of donor full-length KIR2DS4 on aGVHD and cGVHD. These results suggested that combining KIR and HLA genotyping may help make a better sense of transplants in these patients.

Keywords: KIR2DS4; NK cell; acute GVHD; allogeneic hematopoietic SCT; chronic GVHD.

MeSH terms

  • Acute Disease
  • Adolescent
  • Alleles
  • Child
  • Child, Preschool
  • China
  • Cytomegalovirus
  • Disease-Free Survival
  • Female
  • Genotype
  • Graft vs Host Disease / etiology*
  • Graft vs Host Disease / immunology
  • HLA Antigens / genetics
  • Haplotypes
  • Hematologic Neoplasms / genetics
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Incidence
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / immunology
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myelomonocytic, Juvenile / immunology
  • Male
  • Myelodysplastic Syndromes / immunology
  • Neoplasm Recurrence, Local
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Receptors, KIR / genetics*
  • Recurrence
  • Treatment Outcome

Substances

  • HLA Antigens
  • KIR2DS4 protein, human
  • Receptors, KIR