KIR Genes and Their HLA-C Ligands in B-Cell Chronic Lymphocytic Leukemia in a Polish Population.

Abstract

Abstract 4402 IntroductionDysfunction in cellular and humoral immunity entails an increased risk of B-cell chronic lymphocytic leukemia (B-CLL). It has been suggested that innate immunity, especially natural killers cells play key role in antitumor cytotoxicity regulated by interaction between killer immunoglobulin-like receptors (KIRs) on NK cells and some T-cell subpopulations and their HLA-class I ligands on target cells. KIRs receptors have been divided into two functional groups: with long cytoplasmic tails (DL) - inhibitory and with short cytoplasmic tails (DS) - activating. Two broad haplotypes of KIR genes have been defined: the A haplotype characterized by presence of single activating KIR gene (2DS4) and the B haloptype characterized by two or more activating KIR genes (2DS1, 2DS2, 2DS3, 2DS5 and 3DS1).The 2DL2, 2DL3 and 2DS2 KIRs bind to HLA-C1 allotype (Asp80), while 2DL1 and 2DS1 KIRs bind to HLA-C2 allotype (Lys80). Due to lack of representative data in literature the study was undertaken to determine the association between polymorphism of KIR genes and HLA-C allotypes and susceptibility to B-CLL. Patients and methodsThe following KIR genes were typed: 2DL1, 2DL2, 2DL3, 3DL1, 2DS1, 2DS2, 2DS3, 2DS4fl, 2DS4del, 2DS5, 3DS1, in 200 B-CLL patients and 199 healthy individuals using PCR-SSP method. The HLA-C1 and HLA-C2 were determined using Olerup SSP typing kit in 187 B-CLL patients and 104 controls. ResultsIndividual KIR gene content was similar in B-CLL cases and healthy controls although patients with KIR2DS3 gene were more common among cases compared to controls (36% vs. 27%, p=0.06) (Table1). The frequency of AA haplotype did not differ between studied groups (29% vs. 28%). Moreover no differences were found between incidence of HLA-C allotypes (HLA-C1: 74.3% vs. 76.0%, HLA-C2: 67.4% vs.70.2%), genotypes (C1/C1: 32.6% vs 29.8%, C1/C2: 41.7% vs 46,2% and C2/C2: 25.7% vs 24.1) and KIR genes in combination with genes for their HLA-C ligands in B-CLL patients and controls (Table 2).Table 1Frequency of KIR genes in B-CLL patients and controls.2DL12DL22DL32DS12DS22DS32DS4del2DS4fl2DS53DL13DS1B-CLL (n=200)1951061767510854166565318670[%]97.553.088.037.554.027.083.028.026.593.035.0Controls (n=199)1971061808111171162586118178[%]99.053.390.540.755.835.781.429.130.791.039.2Table.2Frequency of the KIR-HLA gene combinations in B-CLL patients and controls.B-CLL (n = 187)Controls (n = 104)N%N%2DL1+/C2+12265.247370.192DL2/3+/C1+13974.337975.962DS1+/C2+4926.202423.082DS2+/C1+7137.974038.462DL1+/C2-6032.083028.802DL2/3+/C1-4825.692524.042DS1+/C2-2211.761817.312DS2+/C1-1910.371110.58 ConclusionsThe data obtain in this study imply that there may be not direct association between KIR and HLA-C gene content in the genome and the presence of B-CLL. Disclosures:No relevant conflicts of interest to declare.