KIR-HLA Signal System Genetic Background of Donor and Recipient Determines Outcomes in HLA-Identical Sibling HSCT.

Objective: To explore the relationship between the background of donor -recipient KIR-HLA and the outcomes in HLA-identical sibling HSCT in Chinese.

Methods: Sequence specific oligonucleotide probes (SSOP) and/or sequence specific primer polymerase chain reproduction (PCR-SSP) was adopted to type HLA, SSP-PCR was used to type KIR. HLA-C1 group is defined as HLA-Cw 01,03,07,08 and related alleles characterized by an asparagine residue at position 80 of the α-1 helix (HLA-C^Asn80) which are recognized by the inhibitory KIR2DL2 and KIR2DL3, and HLA-C2 group is defined as HLA-Cw 02,04,05,06 and related alleles characterized by an lysine residue at position 80 of the α-1 helix (HLA-C^Lys80) which are recognized by the inhibitory KIR3DL1, and HLA-Bw4 group is defined as HLA- B^Bw4 alleles which are recognized by KIR3DL1. KIR-HLA match refers to the presence of at least one recipient HLA allele for the identified donor inhibitory KIR. KIR-HLA mismatch refers to the absence of all the recipient HLA alleles for the identified donor inhibitory KIR. C2 matched group refers to the presence of donor KIR2DL1 and recipient HLA-C2 allele and C2 mismatched group refers to the presence of donor KIR2DL1 and the absence of recipient HLA-C2 allele. Bw4 matched group refers to the presence of donor KIR3DL1 and recipient HLA-B^Bw4 allele and Bw4 mismatched refers to the presence of donor KIR3DL1 and the absence of recipient HLA- B^Bw4 allele. A retrospective study was carried to analyze the outcomes of 59 patients with various hematologic malignancies who received non T-cell depleted transplants from HLA-identical sibling donors. The log-rank statistic of Kaplan-Meier method was used to evaluate the univariate effects on overall survival. Chi-square test was used in comparison of occurrence of aGVHD and the incidence of infections.

Result : Incidence of gradeII–IV aGVHD was significantly lower in patients of KIR-HLA matched group (16/50, 32%)than that in patients of KIR-HLA mismatched group(7/9, 79%)( P=0.01). The incidence of gradeII–IV aGVHD was significantly lower in Bw4 matched group (9/37, 24%) compared to Bw4 mismatched group( 11/18, 61%) (P=0.01). The incidence of fungus infection was significantly lower in Bw4 matched group (5/37,14%) than that in Bw4 mismatched group (8/18,44%)(P=0.01). In myeloid disease, patients with Bw4 matched had much lower incidence of gradeII–IV aGVHD (5/25,20%) comparing with Bw4 mismatched patients(6/10, 60%)( P=0.02) and patients with Bw4 matched also had much lower incidence of fungus infection(3/25, 12%)comparing with Bw4 mismatched patients(8/10, 80%)(P=0.01). Patients with C2 matched had higher overall survival(OS) comparing with C2 mismatched patients (P=0.01).

Conclusions: Donor KIR-recipient HLA genetic background is related with the outcomes in HLA-identical sibling HSCT on incidence of aGVHD, fungus infection and OS. Donor selection referring to Bw4 match may decrease the incidence of aGVHD and fungus infection. Selecting C2 matched donor may improving the OS of patients. The results may offer molecular evidence in optimal donor selection directed by inheritance and may be advisory in clinical therapy.