title: 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.
authors: Department of Experimental Therapy, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. lkarabon@iitd.pan.wroc.pl
authors: L
authors: L
authors: Karabon
authors: A
authors: A
authors: Jedynak
authors: S
authors: S
authors: Giebel
authors: D
authors: D
authors: Wołowiec
authors: M
authors: M
authors: Kielbinski
authors: D
authors: D
authors: Woszczyk
authors: K
authors: K
authors: Kapelko-Slowik
authors: K
authors: K
authors: Kuliczkowski
authors: I
authors: I
authors: Frydecka
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology*; D008024:Ligands; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D054340:Receptors, KIR / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D008024:Ligands; D054340:Receptors, KIR