KIR/HLA gene combinations influence susceptibility to B‐cell chronic lymphocytic leukemia and the clinical course of disease

Abstract

The aim of this study was to analyze the association between gene polymorphisms of killer-cell immunoglobulin-like receptors (KIRs) and their human leukocyte antigen (HLA) ligands and susceptibility to B-cell chronic lymphocytic leukemia (B-CLL) and the clinical course of disease. The distribution of individual KIR genes in 197 B-CLL patients and 200 controls was similar, except for a tendency for lower frequencies of the KIR2DS3 and KIR2DL5 genes among B-CLL patients (26.9% vs 35.5%, P = 0.06, 46.2% vs 55.5%, P = 0.06). The associations between KIR2DS3 and B-CLL reached statistical significance in women (P = 0.05). Moreover, we found a trend toward a lower frequency of genotypes with the presence of five or six activating KIR genes in B-CLL patients compared to controls (20.8% vs 29.0%, P = 0.06), and a significantly higher frequency of individuals possessing genotypes with a prevalence of inhibitory over activating KIR genes (ratio < 0.71) among B-CLL patients (P = 0.04). The HLA-Bw4 specificity was significantly reduced among B-CLL patients (48.7% vs 63.0%, P = 0.005), which resulted from a decreased frequency of HLA-Bw4(Thr80) (21.6% vs 32.0%, P = 0.02). Moreover, among HLA-Bw4-positive individuals, progression-free survival (PFS) tended to be higher in the presence of KIR3DS1 (77% ± 9% vs 39% ± 13%, P = 0.07). However, in B-CLL patients, the presence of HLA-C2 was associated with decreased PFS (49% ± 9% vs 75% ± 7%, P = 0.02), and among HLA-C2-positive patients, the probability of PFS was significantly reduced in the absence of KIR2DS1 (34% ± 11% vs 77% ± 7%, P = 0.007). Our results indicate that the pattern of inhibitory/activating KIR genes, together with their HLA ligands, is associated with susceptibility to B-CLL and affects the clinical course of this disease.

Neuroblastoma patients with high-affinity FCGR2A, -3A and stimulatory KIR 2DS2 treated by long-term infusion of anti-GD2 antibody ch14.18/CHO show higher ADCC levels and improved event-free survival

“…[35][36][37] Since all our 2DS3-positive patients presented also 2DS2, we compared ADCC levels in this combined cohort with 2DS2-positive patients missing 2DS3. Importantly, we did not detect a difference in ADCC levels and EFS between patients with only 2DS2 compared to 2DS2-and 2DS3-positive patients.…”

Killer immunoglobulin-like receptor locus polymorphisms in multiple sclerosis

“…5 Notably, autoantigen-specific cytotoxic CD8 + T cells expressing inhibitory KIRs have been isolated from human blood. [21][22][23] It is therefore conceivable that KIR-mediated inhibitory signals such as those provided by KIR2DL3 regulate NK-and T-cell activation during autoimmune responses in MS. 5,24,25 We observed that individuals carrying two copies for KIR2DL2 but lacking KIR2DL3 were overrepresented in the CIS/MS cohort. Similarly, the frequency of KIR2DL3-negative donors homozygous for KIRD2DS2, with which KIR2DL2 shares strong linkage disequilibrium, was significantly higher in the CIS/MS cohort.…”

Comparison of the KIR3DS1/Bw4 distribution in Chinese healthy and acute myeloid leukemia individuals

“…Previous studies have revealed that coexpression of KIR and particular HLA ligands are associated with leukemia [17][18][19], but rare data was reported in Chinese population. So we compared the distribution of KIR3DS1 and HLA-Bw4 ligands in AML individuals with healthy individuals to investigate the association of 3DS1 gene and HLA-Bw4 with AML.…”

“…It is widely accepted that KIRs, especially the specific KIR-ligand combination, may have associations with leukemia [3,[17][18][19]. KIRD3S1 is one of the main activating molecules which has been conserved during the last several million years.…”