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[The impact of KIR2DS4 gene on clinical outcomes of HLA matched unrelated allo-HSCT].

OBJECTIVE
To detect the frequencies of KIR2DS4 alleles in Chinese Han population and to study the impact of KR2DS4 alleles on clinical outcomes of HLA identical unrelated allo-HSCT.


METHODS
A Sequence-Based Testing (SBT) and TOPO TA cloning system for identifying and distinguishing alleles of the KIR2DS4 gene were established. A total of 150 Chinese-Han individuals, including 75 leukemia patients who received allo-HSCT and their HLA high-resolution typing identical unrelated donors (URD) were entered this study. The patients underwent transplantation for CML (n = 24), AML (n = 19), ALL (n = 29) and other malignancies (n = 3).


RESULTS
The majority (139) of the 150 samples (92.7%) were positive for KIR2DS4. Sequencing of the whole length coding region of this gene identified four of the 12 known KIR2DS4 alleles, KIR2DS4*00101, *003, *004, and *007. 2DS4*00101 was the most frequent, being found in 109 of the 139 individuals (78.4%). The ratio of deleted to non-deleted versions of KIR2DS4 was approximately 1:2. Three novel KIR2DS4 alleles were identified. Transplantations from KIR haplotype B/x donors showed significantly higher overall survival rates than those from KIR haplotype A/A donors [RR 3.1 (95%CI 1.1 - 8.6), P = 0.007]. There was a lower overall survival rates in recipients when their donors carried two 2DS4 full-length allele (2DS4*001) than those carried less (0 or 1) 2DS4*001 allele (P = 0.031). In the haplotype A/A group, a higher risk of acute GVHD (aGVHD) [RR 9.0 (95%CI 1.2 - 66.9), P = 0.01], especially grade III-IV aGVHD (P = 0.006), was seen when the donor was homozygous for the full-length KIR2DS4*00101 allele.


CONCLUSION
The development and application of the described SBT 2DS4 allele typing method highlights the diverse nature of the KIR gene family and displays the existence of KIR polymorphism that remains uncharacterized. Our findings suggest that KIR typing for 2DS4 be beneficial for selecting suitable donors.